Hussain was elected as the Member of the National Assembly of Pakistan for the first time in 2002 Pakistani general election on the ticket of the Muttahida Qaumi Movement from NA-249 (Karachi-XI) constituency and was appointed as the minister of state for Religious affairs and Zakat and Ushar Division in September 2004 in Shaukat Aziz cabinet. As the junior minister of Religious Affairs, Hussain asked religious scholars from Pakistan to issue a 'Fatwa' regarding suicide bombings in May 2005. In June 2005 he was attacked by enraged youths during his visit to Jamia Binoria. Police however denied that any incident of manhandling of Hussain had taken place and said that the crowd only chanted slogans. Hussain was the minister of state for Religious Affairs until July 2007, when his party asked him to resign from his position as Minister of State for Religious Affairs and from his seat as a member of the National Assembly. According to an official statement, the party was unhappy with the statements made by Hussain against Salman Rushdie. In 2007, he resigned from politics. Later in 2008, MQM also expelled him from the party.