The endorsement, which was announced at a press conference in Gaza City, will increase the likelihood of al-Barghuti finishing runner-up to PLO chairman Mahmud Abbas in the 9 January poll to succeed the late Yasir Arafat as president of the Palestinian Authority.
"We are appealing to our members, cadres and supporters to support the candidacy of Mustafa al-Barghuti and vote for him," Rabah Muhanna, a member of the leftist organisation's politburo, said.
The PFLP, which boycotted the only previous presidential election in 1996, had announced in November that it would participate this time round but would not be presenting a candidate.
Al-Barghuti, 51, a democracy and human rights activist, has been running a distant second to Abbas who is the candidate of the dominant Fatah faction.
Abbas' path to victory was effectively cleared when the resistance movement Hamas announced that it was boycotting the ballot and the jailed intifada leader Marwan al-Barghuti (no relation to Mustafa) dropped out of the race.