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Jilani commenced practising law in 1979, while Pakistan was under martial law.
Jilani is internationally recognised for her expertise in critical human rights investigations. In February 1980 with her sister Asma Jahangir, she co-founded Pakistan's first all-female legal aid practice, AGHS Legal Aid Cell (ALAC) in Lahore. Initially the activities were confined to providing legal aid to women, but gradually these activities increased to including legal awareness, education, protection from exploitation, legal research, counselling and providing legal assistance as well. She is also one of the founders of the Human Rights Commission of Pakistan and the Women's Action Forum (WAF) (a pressure group established in 1980 campaigning against discriminatory legislation) and also founded Pakistan's first legal aid center in 1986. In addition to providing pro bona legal aid, she has also helped set up a shelter for women fleeing violence and abuse, called Dastak in 1991. In addition to managing a shelter, Dastak also organises workshops to create awareness of human rights and the protection of women.
A lawyer and civil society activist and active in the movement for peace, human rights and women's rights in Pakistan for the last three decades, she specialises in human rights litigation, and is especially concerned with the human rights of women, children, minorities, bonded and child labour, political and other prisoners. She has conducted several cases which have become landmarks in setting human rights standards in Pakistan. Her battle for the rights of children, especially the protection of child labourers engaged in hazardous work, led to the promulgation an act regulating the employment of children in 1991.
Jilani is often invited to speak at various events pertaining to human rights. On 17 September 2009, she delivered the 2009 Hal Wootten Lecture, at the Faculty of Law at the University of New South Wales. On 25 November, she was invited as guest lecturer at McGill University's Faculty of Law, the McGill Centre for Human Rights & Legal Pluralism, on the topic of "The Promise of International Law for Civilian Victims of War: The Goldstone Report". On 27 November 2009 Jilani was invited as a speaker at the Halifax International Security Forum in Canada on "Law vs. Power: Who Rules? Who Makes the Rules?".
Jilani is also affiliated with the United Nations Human Rights Council, the Carter Center, and the UN Conference on Women.
From 2000 to 2008, Jilani was the United Nations Special Representative of the Secretary-General on Human Rights Defenders. During that period, she was also appointed to the International Commission of Inquiry on Darfur, Sudan, in 2006.
In 2009, Jilani was appointed to the United Nations Fact Finding Mission on the Gaza Conflict.
In 2017, Jilani co-chaired (alongside Tarja Halonen) the World Health Organization/Office of the United Nations High Commissioner for Human Rights High-Level Working Group on the Health and Human Rights of Women, Children and Adolescents.
In addition, Jilani holds the following positions:
As a result, their work in the field of women's activism, Jilani and Jahangir have been arrested, received death threats, and faced hostile propaganda, intimidation, public abuse and murder attempts on themselves and their family. In 1999 after representing the case of Samia Sarwar, a young woman who was seeking divorce from her abusive husband, Jilani and Jahangir were again subject to death threats. Samia's mother came with a gunman to her office on the pretext of seeking reconciliation with her daughter. The gunman shot Samia dead and fired at Hina who managed to escape. Another time, gunmen entered her house and threatened members of her family. She herself was away from home: the threats put pressure on her to migrate, but she refused, and continues to live and work in Lahore.
"The problem with the cases of honour killings and their non-prosecution lies in the permission that the law grants to the family of the victim to compromise the offence, and that's why the person who actually pulls the trigger walks free... although in the case of honour killing it's mostly a conspiracy between more than one member of the family, and that's the major issue here. I don't think the government wishes to address that issue."
"I always had this feeling that if you see injustice, you have to speak out against it; otherwise you are not in a position to complain."
"It was anger against state-sponsored injustice that forced me to enter courtrooms in the 1970s. [...] For all these years I have retained that outrage so I have been able to fight for human rights and against bonded labour, blasphemy laws..." (Monday, 15 March 1999, in Tribune India)
"The right to life of women in Pakistan is conditional on their obeying social norms and traditions."
"There is a real danger of this occurring. The military have an agenda of supporting the extremists and are ideologically very akin to the extremists. It is very important that the world understand how important it is to act in a wise way."
"The United States totally misread the situation. If Musharraf had been successfully countering terrorism, we would not have a situation eight years down the road where (terrorists) actually control territory. Nobody has tried to find the source of the money or the source of the weapons."
"When you put them on trial, you show the wickedness of their crime. Once it becomes abundantly clear that the terrorists' victims are almost entirely comprised of Pakistani civilians, only then will sympathy for their cause be lost. We have to deal with terrorism as a criminal element."
"The civilian government must be supported thoroughly, otherwise we will lose it."
"The administration of justice can be severely hampered if laws emerge from different understandings or perceptions of religion, and their application becomes uneven because of the religious, moral and social beliefs of those administering these laws. Islam and almost all other religions of the world have sectarian and denominational differences. If a national polity is founded on religion, these differences will be manifested in political tensions as well as oppressive restraints on dissent."