Renzi, who became premier in February 2014, has staked his leadership on the outcome of the vote, which is due to be held in either October or November.
In that respect, many are comparing it to the UK's referendum on leaving the EU, which was called by ex-British Prime Minister David Cameron. Cameron stepped down on June 24th, the day after the country voted to leave the bloc, immediately causing political and economic chaos.
But in an interview with CNBC, Renzi said: “I am sure we (will) win. This referendum is about the future of the country and I am sure the Italian people, if (they) read the question in the ballot in the electoral place, will vote for change."
The ''Yes' or 'No' referendum on which Renzi is betting his political future intends to bring about reforms that would streamline Italy's political system, which basically means getting laws passed quickly and stabilizing future governments.
The reforms are much-needed. But now the important decision has been left in the hands of Italians after parliament failed to reach the maximum support required to avoid sending it to a public vote.
But with many failing to grasp Italy's complex political systems, the vote could be a chance for people to simply say "Yes" or "No" to Renzi as the country's leader.
He was evasive when asked by CNBC about whether he would resign if he lost the vote, instead repeating: “I will win”.
"Our strategy in the next weeks will be (to promote the fact that) this is not Renzi's referendum. This is a referendum," he added.
In a report on Friday, the political risk consultancy firm, Eurasia Group, said the referendum had a 60 percent probability of passing, but added that the polls have narrowed sharply since April.
Meanwhile, the eurosceptic Five Star Movement, the second-biggest party in parliament, is gathering popularity, scoring a milestone victory in the second and final round of local elections in June. The party's Virginia Raggi was elected Rome's first female mayor, and Chiara Appendino was elected Turin's third female mayor.
In its report, Eurasia said a ‘No' vote could cause Renzi's government to collapse.
"A debilitated Renzi would come under intense pressure to resign; he may himself not wish to cling on to power," analysts Federico Santi and Mujtaba Rahman wrote.
Renzi added that the prospect of the Five Star Movement leading the country should prompt people to back him in the vote.
“[If we don't win] people need to understand that instability would follow,” he said.
“Not only would short-lived governments remain, but there is also the risk, if you look at the polls, that the Five Star Movement could go on to lead the country. Do [people] want change, and finally choose the future, or do they want to continue with the same model, and destroy the prospects for growth made over the last few years?”