Mark Ruffalo has shared the screen with Leonardo DiCaprio, Sean Penn and the almighty Thor. But for his latest project, he faced the most daunting co-star of his career: himself.

In “I Know This Much Is True,” debuting Sunday on HBO, the three-time Oscar nominee plays Dominick, a short-tempered house painter, as well as his twin brother, Thomas, whose battle with paranoid schizophrenia lands him in a mental institution after he chops off his own hand.

Much of the six-part miniseries deals with Dominick’s efforts to get his sibling released. Along the way, he’s forced to confront family secrets and decades of guilt, leaning on a support system that includes a straightforward social worker (Rosie O’Donnell) and an infinitely patient psychologist (Archie Panjabi).

It’s a performance that’s guaranteed to earn Ruffalo an Emmy nod. Maybe even two.

“I love the guy,” said director Derek Cianfrance (“Blue Valentine”), who also co-wrote the screenplay adapted from Wally Lamb’s novel. “I’m a filmmaker who likes to explore the harsher, darker sides of the human soul and with Mark I can put him in situations that are deeper because he’ll naturally rise out of it. It creates a nice dichotomy. There’s no one else on the planet that could play these two guys.”

To pull off the feat from a technical standpoint, Cianfrance shot his star as Dominick for 15 weeks, followed by a five-week period in which he filmed various flashbacks. During that break, Ruffalo put on 30 pounds to reflect how Thomas’ medication had made him doughy.

“Putting on the weight for Thomas was really challenging,” Ruffalo said in January. “I didn’t expect it to be. I thought I was going to be having a fun time doing that. But when you’re force-feeding yourself, some of the romance of food sort of leaves.”

He also used the time to grasp a better understanding of mental illness.

“Those five weeks were actually kind of lonely,” Ruffalo said. “You want to be honest with what’s going on in that world and getting to know it and getting comfortable with it. From that aspect, it was more challenging than playing Dominick. I was really afraid to play it, to be honest with you.”

The Wisconsin-born Ruffalo has always been a fearless actor, starting with his breakthrough role in Kenneth Lonergan’s 1996 play “This Is Our Youth.”

Lonergan would later cast him in the critically acclaimed film “You Can Count on Me,” which was followed by hits like “13 Going on 30,” “Now You See Me” and “The Avengers” franchise, in which he played both the Incredible Hulk and Bruce Banner, his first taste of doing double duty.

But “True” is his most impressive showcase to date. While both of his characters get a chance to rant and rave, he is even more moving in the quiet moments.

In the scene where Dominick says goodbye to his dying mother (Melissa Leo), Cianfrance shot him so that the audience only sees his right eye. Ruffalo expresses more with a few blinks and tears than most actors could do with a dozen tantrums.

“I want to be the kind of artist who can’t be labeled, who surprises people and surprises myself and sometimes screws it up and sometimes makes it work,” he said. “I want to keep challenging myself so I’m not dead.” Twitter: @nealjustin