The winger had just received a pass from fellow Mexico international Erick Guiterrez, who had recently entered the contest, when he was caught by Willem II's Freek Heerkens.
Lozano went down awkwardly after the tackle and though no foul was called on the play, the attacker appeared to injure his knee during the incident.
He was treated on the field for a few minutes before a stretcher was summoned, with Lozano departing the game in apparent pain.
Gaston Pereiro replaced him officially in the 84th minute, while goals from Donyell Malen, Michal Sadilek and Steven Bergwijn ensured PSV remained level with Ajax on points in the Eredivisie title race.
After the match, PSV head coach Mark van Bommel admitted he didn't know the severity of the injury and will have to wait until tests are completed Friday.
"I can't say anything about it right now," Van Bommel told Fox Sports. "All I can do is hope it's not bad. It's difficult to predict the damage because I couldn't see the accident happen. The linesman stood right in front of me."
Heerkens also spoke of the incident following the match, saying he apologised to Lozano, which the Mexico star accepted.
"He accepted my apologies and knew I didn't hit him on purpose," Heerkens said. "The ball was played a bit to slow and it was my intention to slide before he was there, but he stood there and my left leg hit him. I don't know if he's seriously injured, because he was in one of those machines..."
It is the second time this season Lozano has been taken off via a stretcher after an injury.
Against Groningen on January 26, the attacker went down after a clash of heads and was examined at a hospital before being released the next day.
He would miss one match before returning to the field against Utrecht on February 10.
The star man has enjoyed another strong season in the Eredivisie for PSV, having scored 17 goals and adding eight assists this season in 30 games – exactly matching his output from his debut season in Dutch football last year, coming in 29 games in 2017-18.
Lozano also added two goals and an assist this season in the Champions League for PSV, though it was not enough to see the side through to the knockout stage of the competition.
Mexico head coach Tata Martino supports such a move, saying in March that Lozano was "ready" for the step up to a top-five league.
Lozano himself has openly spoken of his desire to one day play in the Premier League, admitting in November he hoped God would give him a chance in the English top flight.