Prime Minister Matteo Renzi says his proposed reforms will streamline the Italian government, reduce bureaucracy, and make it easier to pass laws.
Critics say changes to the constitution will remove checks and balances and give more power to the ruling party.
A "no" vote in Sunday's referendum will not only block Renzi's reforms, but could also mean the end of his premiership.
He's promised to resign if voters reject the changes.
Many Italians see the referendum as an opportunity to punish the establishment.
Comparisons are being made with the victory of Donald Trump in the United States and Britain's Brexit vote to leave the European Union.
What happens in Rome if there's a "no" vote?
And how would Italy and the EU be affected?
Presenter: Adrian Finighan
Massimo Franco, Newspaper columnist for Corriere della Sera
Matt Qvortrup, Joint Editor of European Political Science Review and author of Referendums Around the World and Referendums and Ethnic Conflict
Alan Friedman, Journalist and author of Berlusconi: The Epic Story of the Billionaire Who Took Over Italy
Source: Al Jazeera News