The party, Un Nuevo Tiempo, said it will back Pablo Perez, the governor of the western state of Zulia, as the best hope to deprive Chavez of a third term.
"I'm sure the party and Venezuelans together can move this great country forward," Perez wrote on his Twitter account after the announcement was made by party leader Manuel Rosales, who has been in exile in Peru since April 2009.
Zulia is Venezuela's most populous state and the center of the country's lucrative oil industry.
Perez, 41, joins Miranda state governor Henrique Capriles, Caracas mayor Antonio Ledezma and opposition lawmaker Maria Corina Machado in the field of candidates seeking to replace Chavez.
Rosales, who lost to Chavez in the 2006 presidential election and now stands accused of corruption, said he could not return to Venezuela to run for office any time soon.
"It's not my time, it's my country's time," he said.
Chavez, who was diagnosed with cancer in June and has so far undergone two rounds of chemotherapy in Cuba, has repeatedly said he will seek a third six-year term.
Copyright AFP (Agence France-Presse), 2011