ST. LOUIS — Matt Cain and Matt Holliday go way back.

In the case of Holliday, it was way, way, way back.

Holliday’s solo homer off Cain on Aug. 29, 2005, marked the first run ever scored off the future Giants ace.

They have faced each other 46 more times since the pitcher’s big league debut, but never with this much at stake — and never with this much drama.

Cain faces the St. Louis Cardinals’ newly minted villain Wednesday in Game 3 of the National League Championship Series. And there’s already speculation about a brush-back pitch in the wake of Holliday’s controversial slide into Marco Scutaro.

Asked on Tuesday if he was worried about the extra scrutiny on his inside fastballs, Cain shrugged.

“If something gets away from you inside, that’s part of the game,” he said.

Holliday left Scutaro with an injured hip when he came into second base hard and — by his own admission, late — to break up a double play in Game 2. Giants manager Bruce Bochy on Tuesday reiterated his assertion that the slide was “illegal” while his Cardinals counterpart Mike Matheny said Holliday was “trying to play the game hard.”

Regardless of the interpretation, Cain needed no introduction to the six-time All-Star. The only right-handed batters he has faced more often in his career are the Colorado Rockies’ Troy Tulowitzki (58 plate appearances) and the Arizona Diamondbacks’ Justin Upton (55).

Holliday’s career results against Cain are a mixed bag: 8 for 40 with three home runs, six RBIs, four walks, six strikeouts — and, ahem, one hit-by-pitch.

“I’ve been a guy that’s always go to challenge him, and he’s a guy that’s going to challenge you at the plate,” Cain said Tuesday before a workout at Busch Stadium. “He’s not afraid to swing the bat.”

Cain said the key to his approach against Holliday is location. Because the 6-foot-4, 235-pounder swings hard, mistakes can be extra costly.

“It’s not going to be for a little sloppy single,” he said. “It’s going to be something that is going off the wall or over it.”

Proper command is a legitimate concern for Cain, who has not been sharp in the postseason. In two starts against Cincinnati in the N.L. Division Series, he had a 5.06 ERA and gave up three home runs in just 10﻿2/3 innings.

Another sore spot: Cain is 0-2 with an 8.27 ERA in three career starts at new Busch Stadium. Asked about that Tuesday, the pitcher pointed to one miserable start here in 2008, when he gave up nine runs in 3﻿2/3 innings.

“(Albert) Pujols took me to Big Mac Land,” Cain said, recalling a home run Pujols hit into the left field’s second deck. “I remember that one was not good at all.”

Instead of casting his memory back that far, Cain preferred to look back only as far as Monday night. That’s when Giants teammate Ryan Vogelsong delivered the moment the Giants rotation has been waiting for: seven innings of one-run ball.

For a staff expected to carry the load, Vogelsong’s start represented a return to normalcy.

“That was big for us,” Cain said. “We haven’t been pulling our weight as a starting staff. And Vogey did a really good job of that. We all definitely needed that. Hopefully, that right there sparks us to all pitch as well as he did.”