The world number four is looking for his third Masters title and hoping to bounce back from the disappointment of his final loss to John Isner in Miami.
The Spaniard will face Grigor Dimitrov in the last four on Saturday.
The 26-year-old Bulgarian booked a last-four clash with either defending champion Rafael Nadal or Austrian Dominic Thiem.
Matches will be available to watch live and on demand for members of Amazon Prime Video, its internet video service.
The Spaniard needs to win the Monte Carlo title to stay clear of Roger Federer at the top of the world rankings
Second seed Marin Cilic is also into the last eight, after Milos Raonic pulled out with a right knee injury before their third-round match
Belgian sixth seed David Goffin held off a late fightback from Roberto Bautista Agut to reach the last eight.
Federer is missing the claycourt season for the second year in a row, but Nadal says he has no plans to skip any Grand Slam tournaments in the near future.
The Serb is working with long-time former coach Marian Vajda for the first time in almost a year after splitting from Andre Agassi, and has looked rejuvenated in Monaco.
The former world number four will face either Guillermo Garcia-Lopez or Andreas Seppi for a place in the quarterfinals.
The two-time French Open semifinalist recovered from a set down to book a last-16 clash against either Novak Djokovic or Borna Coric with a 5-7, 7-5, 7-5 victory.
The 30-year-old also played down reports of a rift between him and Agassi, thanking the American for "helping his career" over an 11-month period.
It was the 12-time Grand Slam champion's first win at a regular ATP Tour event this season.
In a battle of two former Grand Slam finalists, Nishikori raced through the final two sets to progress with a 4-6, 6-2, 6-1 victory.
The 27-year-old, who tested positive for cocaine last April, has been handed a wildcard into the qualifying draw for the tournament, which starts on April 28.