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Santhanam was born on 21st January 1980. He resides in Pozhichalur , Chennai.  He has a Diploma in Electronics and Communication Engineering from Meenakshi Krishnan Polytechnic College.

Santhanam started his career in television and his fame started off with Lollu Sabha in Vijay TV. He made his feature film debut with sachin in 2004 and later appeared in several successful films. Though is considered his first feature film, he has acted in two films before Manmadhan. He was also in STR's debut film as a leading actor, namely Kadhal Azhivathillai. 

He is best known for his roles in Siruthai and director M. Rajesh's comic trilogy, comprising Siva Manasula Sakthi, Boss Engira Baskaran and Oru Kal Oru Kannadi, the former two earning him the Vijay Award for Best Comedian for their respective years. After Manmadhan, Santhanam continued his collaboration with actor Silambarasan, appearing in successful comedy tracks in Vallavan, Kaalai, Silambattam, Vaanam and Osthe. 

He has started a film production company named Handmade Films.
In recent times Santhanam is titled as the comedy super star of Tamil Cinema. Most of the directors depend on him to ensure box-office success.