The by-election to the Madurai West assembly seat on Tuesday will see a straight fight between the Congress candidate, backed by the DMK, and the AIADMK.
The election was necessitated following the death of AIADMK legislator SV Shanmugam in February.
The constituency has 156,182 voters, with more women voters than men.
For the AIADMK, Madurai district secretary 'Sellur' K Raju, a local from the backward Mukkulathore community, is the party candidate.
The Congress claims the chances of its candidate - KSK Rajendran - winning are very good. The DMK has decided to support the Congress candidate, who is also from the Mukkulathore community.
State Congress leader M. Kriashnaswamy said: "The victory of the Congress candidate is sure and his win will define the prestige of the UPA (United Progressive Alliance) coalition."
Madurai and other southern districts are the stronghold of DMK leader MK Azhagiri, Chief Minister K Karunanidhi's son.
Madurai West is an AIADMK stronghold, with the party winning it four times before.
As many as 2,500 security men, including six battalions of paramilitary forces, have been deployed on security duty. Central forces, armed police and Rapid Action Force are monitoring the constituency.
Counting will take place June 29.