"The people of Tamil Nadu will never support a coalition government," she said.
Jayalalithaa, who is contesting from Srirangam in Trichy, said the people of the state are "thoroughly disgusted" with the domination of a one single family in the affairs of the state.
"The people have made up their mind to throw out this family lock, stock and barrel," she said in response to a query.
Her comments come days after Karunanidhi indicated that the DMK may head a coalition government in the state if the situation warrants.
The Congress, which has been providing outside support to the DMK Government in Tamil Nadu, has also been indicating that it may join the government if the combine is voted back to power.
"The results will speak," Jayalalithaa, who is hopeful of making a comeback in the elections, said.
The former chief minister also lamented that there was little time left for campaigning as the Election Commission decided to conduct the polls in April instead of May.