The Greek-majority is due to join the European Union, but Saturday's vote will determine whether the country joins as a whole.
Early indications were that the Turkish north will support the UN reunification plan, but their referendum will mean little if Greek Cypriots reject unity.
Voters on both sides must approve the plan if it is to be implemented.
Diplomats are worried a Greek veto will put paid to years of international pressure to reconcile the two parts of the island.
The island was split after an invasion by Turkish troops in 1974 in response to an attempted coup that sought to annex Cyprus to Greece.
UN plan details
The plan developed by UN Secretary-General Kofi Annan envisages a loose federal structure for the island.
Many Greek Cypriots refugees who fled the Turkish assault would be allowed to return and recover some of the land they lost.
UN peace plan for Cyprus
Greece, Turkey and UK would remain guarantors of island's independence
Maximum 45,000 mainlanders would stay on either side with new limits for ethnic cross-dwelling
Turkish Cypriot territory would be reduced by 7% to allow back 120,000 Greek Cypriots under Greek Cypriot administration
Turkey would maintain a cut-back troop presence in Cyprus
Cyprus would be governed by a nine-member presidential council of six Greeks and three Turks, three of whom would have no voting rights
But Turkish troops would be allowed to maintain a reduced garrison on the island.
Greek Cypriot President Tassos Papadopoulos and his Turkish counterpart Rauf Denktash have both rejected the plan.
However, if opinion polls prove correct, Turkish Cypriots are likely to support the plan and their southern neighbours reject it.
Criticism and disagreement
The EU has attacked Papadopoulos for urging his electorate to reject a plan which he appeared to have been backing until recently.
In a final blast at what the EU regards as Greek Cypriot intransigency, Enlargement Commissioner Guenter Verheugen said Greek Cypriot fears of losing tourist dollars were behind their opposition.
Papadopoulos casts his vote
The wealthy hotel owners in the south fear "that the north that is not very developed for tourists, but in reality is more attractive, could become competition for them", he said.
But Russia has come out in Papadopolous' favour, accusing the UN of granting too many concessions to the Turks.
Russia used its veto powers on the UN Security Council to block a proposal for a neutral force to help police the island, were it to be reunified.
The proposal's backers said it was intended to reassure Greek Cypriots that they would not face a threat from Turkish soldiers - but Russia argued it was an attempt to influence Saturday's vote.
"The Greek Cypriots are saying that they don't gain anything from the unification plan since their place in Europe is assured," said Turkish Cypriot analyst Yusuf Kanli.
But he warned the stance could backfire.
"If the Greek Cypriots insist on their position the first consequence will be a gradual relaxing of the economic embargo on Turkish Cyprus," he said.
"In the long term it will be the start of international recognition of a Turkish Cypriot state. They could end up with a permanent internationally recognised Turkish Cyprus."