Handique, 82, who was admitted to Jorhat Medical College and Hospital for heart-related problems only yesterday and shifted to ICU, died this afternoon, a hospital spokesman said.
The veteran Congress leader, who was born in 1933, leaves behind his wife and three daughters.
Handique was the Minister for Mines and Development of North Eastern Region in the UPA-II government.
He also held the portfolios of Union Minister of State for Defence, Parliamentary Affairs, Mines, and Chemicals and Fertilizers during the tenure of the UPA-I government.
He was also a member of Rajya Sabha from 1980 to 1985 and a member of several parliamentary committees.
Handique, first elected to Assam Legislative Assembly in 1972, became an AICC member in 1973 and Congress Working Committee member in 2002.