Thyagarajan was born in Chennai. His first language is Tamil. Thyagarajan has a sister, Preeti. Thyagarajan married Grahalakshmi, the daughter of a Chennai industrialist, on September 1, 2005. The couple divorced three years later.
Thyagarajan studied Computer Graphics and Multimedia and went to Trinity College of Music in London before embarking on an acting career. He completed his 12th grade and was enlisted in two medical college.
Prasanth Thyagarajan debuted in 1990 in the film Vaigasi Poranthachu when he was 17 years old. His other notable films include Balu Mahendra's Vanna Vannna Pookal and R.K. Selvamani's Chembaruthi, both released in 1992.
In 1998, Prasanth Thyagarajan appeared in S. Shankar's film Jeans. Later, he appeared in such films as Kannathirey Thondrinal, Jodi and Parthen Rasithen.
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