Mani, 45, was undergoing treatment for liver and kidney diseases at the Amrita Institute of Medical Sciences.
"Sad about my friend Kalabhavanam Mani. One more of My Malayalee brothers dying of cirrhosis. He had more talent than time," Haasan, 61, posted on Twitter.
Mani starred in over 200 films, including Malayalam, Tamil, and Telugu films, and is especially known for his character and villain roles.
He won the National Film Award and Kerala State Film Award in 1999 for his performance as Ramu in "Vasanthiyum Lakshmiyum Pinne Njaanum".