Khachanov, of Russia, fired six aces and benefited from three double faults by his opponent to dispatch the Italian in 88 minutes.
Top-seeded Andrey Rublev of Russia cruised past France's Richard Gasquet 6-3, 6-4. The third seed, Ugo Humbert of France, also sailed through to the quarterfinal round with a 6-4, 6-1 win over Pavel Kotov of Russia.
Fourth-seeded Alexander Bublik had a tougher time in his match against Marton Fucsovics of Hungary. The Kazakhstan native overcame six double faults and rebounded from a first-set misstep in his 2-6, 6-3, 6-4 win.
Also Wednesday, Alexei Popyrin of Australia notched a 7-6, 7-6, 6-1 victory over Frenchman Hugo Grenier, and Finland's Emil Ruusuvuori posted a 6-3, 6-3 win over Christopher O'Connell of Australia.
Former world number one Andy Murray fell in a tough three-set match to Czech 18-year-old Jakub Mensik, who ousted fifth seed Alejandro Davidovich Fokina of Spain in the first round. Mensik needed three hours and 26 minutes to beat Murray 7-6, 6-7, 7-6.
France's Gael Monfils eked out a 4-6, 7-5, 7-6 victory over China's Zhang Zhizhen.
Rio Open
17-year-old Brazilian Joao Fonseca posted the first ATP Tour victory of his career, upsetting seventh-seeded Frenchman Arthur Fils 6-0, 6-4 in the first round in Rio de Janeiro.
Fonseca, the reigning US Open boys champion, is ranked 655 in the world, while Fils is ranked 36th. Fonseca never faced a break point and won 68 per cent of the points on Fils' second serve.
Only one other match was completed on Wednesday in a rain-interrupted slate. Fourth-seeded Francisco Cerundolo of Argentina routed Spain's Albert Ramos-Vinolas 6-2, 6-1.
Los Cabos Open
The United States' Alex Michelsen scored a second-round upset in Los Cabos, Mexico, eliminating third-seeded Alex de Minaur of Australia 6-4, 6-1.
The players' serves dictated the outcome, as Michelsen had a 62 per cent first-serve rate while de Minaur put just 38 per cent of his first serves in play.
Second-seeded Stefanos Tsitsipas of Greece, fourth-seeded Casper Ruud of Norway and eighth-seeded Jordan Thompson of Australia all cruised to straight-set wins, while Portugal's Nuno Borges got past seventh-seeded Max Purcell of Australia 6-3, 6-3. Aleksandar Kovacevic of the United States also advanced.
In night action, top-seeded Alexander Zverev of Germany trounced Japan's Yoshihito Nishioka 6-3, 6-0, and Australia's Thanasi Kokkinakis downed Great Britain's Daniel Evans 6-4, 6-2.
