Azerbaijan and the international community do not recognise Nagorno-Karabakh's independence and Azerbaijan's foreign ministry said in a statement that holding the referendum "may impede the peace process".
It said: "Azerbaijan does not recognise the results of the referendum, which contradicts efforts to achieve lasting peace and stability in the region."
On December 10, 1991, the self-styled Nagorno-Karabakh Republic declared independence from Azerbaijan, but despite having its own flag, military and government, remains unrecognised as a separate state by other countries, including Armenia.
Nagorno-Karabakh's separatist government continues to seek recognition. The majority of people in Nagorno-Karabakh are Christian ethnic Armenians who associate themselves with neighbouring Armenia rather than Azerbaijan, a majority Muslim state.
Azerbaijan wants to restore its control over the region and said the referendum was illegitimate.
Sporadic clashes inside the territory between Azeri and ethnic Armenian fighters began in 1988 and escalated to full-scale hostilities in 1992 between Azeri forces and troops from the neighbouring state of Armenia.
About 35,000 people have died in the conflict and up to one million people have been displaced.
A ceasefire was signed in 1994 but a peace deal has yet to be successfully brokered.
The Karabakh vote follows similar polls in a number of other unrecognised former Soviet Union states, including Georgia's breakaway South Ossetia and Moldova's Transdniestr earlier this year.