In an interview on Italian radio, the premier said: "I'm here to change things. If that doesn't happen, there is no role for me to play."
If the 'No' vote wins on December 4th and Renzi's proposed changes to the constitution are rejected, it is likely that a temporary or technical government will be formed to change the electoral law before general elections can be held.
The PM said he would not be willing to seek a deal with other parties to form a coalition if this happens, adding that he didn't want to take part in "old-style political games".
Renzi vowed to "fight like a lion" to win the vote and said he believed the "silent majority" of voters would back him in the referendum. He is currently touring the south of the country, where the 'No' camp's lead is strongest.
However, he also emphasized that he didn't envisage a 'No' victory causing immediate problems in the country.
"The 5th of December won't be Armageddon," said Renzi. "If 'No' wins, everything will stay as it is. Italians shouldn't be fooled by politicians who are fighting to keep the privileges they have always had."
The reforms would see the number of senators and their legislative power drastically reduced, which Renzi claims will cut down on bureaucracy, making government more stable and efficient. But his opponents argue that there are inconsistencies in his proposed changes, and that they would put too much power in the hands of the prime minister.
Early on in the campaign, Renzi repeatedly said that he would resign if defeated, a vow intended to emphasize how 'ungovernable' he believes Italy is under the current constitution.
But as the opposition joined together to challenge the reforms, and framed the vote as a chance to express dissatisfaction with Renzi's government and the political establishment, he back-tracked from this promise.
The premier admitted it had been a "mistake" to personalize the reforms and in later interviews refused to confirm the pledge to quit. He has also sought to dial down the impact of a possible 'No' victory in the vote, which global media have framed as 'the next challenge to the political establishment'. He said last month that he did not "anticipate any major disasters" in the event of a 'No' win, but reiterated that he would do "everything" to ensure this did not happen.
Polls published in recent weeks show the 'No' camp ahead by an increasing margin, however both opinion polls and bookmakers were wrong in their predictions of the UK's EU referendum and the recent US presidential elections. Furthermore, the lead for 'No' is strongest in the south of the country, which typically has a lower voter turnout, and polls do not include undecided voters.