She was 51.
Kalpana Ranjani was in Hyderabad for shooting a Telugu film and was scheduled to leave for Kerala later today.
She was declared brought dead at a hospital around 7 am, sources told PTI.
Kalpana had received National award in the best supporting actress for her performance in "Thanichala Njan" (2012).
Sister of actor Urvashi and Kalaranjini, Kalpana forayed into the Malayalam films as a child actor in "Vidarunne Mottukul" in 1977.
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Among her other Malayalam hits are "Ennum Eppuzhum", "Karnavar", "Dolfins", "Bangalore Days" and "Spirit".
The actress' body is expected to be brought to Kerala later today. She is survived by her daughter.
Malayalam actors K P A C Lalitha, Kaviyoor Ponnamma and Innocent, MP, expressed shock at the demise of the actress, who was best known for her comic roles in South Indian films.