Outfielder Mitch Maier is being recalled from Triple-A Omaha to replace Guillen on the roster, Hillman said.
Guillen was preparing for his first at-bat in Wednesday night's game, a 9-6 loss to the Angels, when he felt a pop in his knee and felt severe pain. He was taken to a hospital for evaluation and then visited the team doctor on Thursday.
The Royals said there was a Grade 2 tear in the lateral collateral ligament and a strained muscle behind the right knee. Guillen is expected to be out six to eight weeks. It's not known if surgery will be necessary.
The Royals have a ready replacement in Mark Teahen, who gave up the third-base spot when Alex Gordon returned from the disabled list after the All-Star break. Teahen had been moving around since the second half began, but he was the club's regular right fielder in the 2007 season.
Teahen is one of the Royals' leading hitters, with a .296 average, nine homers and 34 RBIs.
The Guillen news came just before Hillman arrived at the Royals' off-day Diamond of Dreams benefit event at Kauffman Stadium.
"They just keep coming," Hillman said.
The Royals already have lost center fielder Coco Crisp and shortstop Mike Aviles for the season, and Gordon just returned after missing 79 games.
Also on the disabled list are starting pitcher Gil Meche and relievers Kyle Farnsworth and Doug Waechter. Meche might come off the DL soon, but Farnsworth is likely weeks away. Waechter is rehabbing with Omaha and has a 6.75 ERA in eight games.
This is the second DL stint for Guillen this season. He was out with a groin injury from April 10-25. Bothered by aching legs much of this season, he had struggled at the plate and in covering ground in right field. In 79 games, he was batting just .245 with nine home runs, eight doubles and 40 RBIs.
Last season, Guillen also battled leg miseries but fought going on the DL and matched his career high of 153 games while hitting 20 homers with 97 RBIs and a .264 average.
Maier has a .314 average in 12 games with Omaha, and this is his second callup this year. The first came on April 16, when Gordon was disabled, and Maier played in 64 games with a .213 average and nine RBIs. He was sent back to Omaha six days ago.
The Royals will resume play and try to snap their nine-game losing skid on Friday night against the visiting Texas Rangers.
Dick Kaegel is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.