For the hugely popular Mexican comedian Eugenio Derbez, making people laugh comes naturally; making them cry – or at least making himself shed a tear – is a different story.

Which is exactly what he had to do as the star of “No eres tú, soy yo” (“It’s Not You, It’s Me”), a box-office hit in Mexico last year that opens in the city Friday at Village East Cinema, 189 Second Ave.

“My work has always been tied to comedy, and this time I had to cry and be on the screen practically all the time,” says the Mexico City resident. “I got so much into my character that I would get home depressed.”

Derbez, 49, plays Javier, a husband who goes through a major meltdown after his wife leaves him. He weeps easily, becomes depressed and ends up in therapy in his quest to get over María.

“Making the film was very interesting because it allowed me to discover other dimensions of acting,” he says in Spanish. “I went back to acting classes, to be able to register the emotional levels I needed for this role.”

Yet, in a sense, the character is a return to his first steps as an actor when he had his eyes on a dramatic career. That changed in 1988, when he started working on a Mexican TV comedy show, “Anabel.”

“Everyone started to tell me that I had the skill to make people laugh, and I ended up understanding that that was the case,” he explains. “Comedy arrived late in my life.”

He has since created 14 characters and authored two books of comedy. He currently produces and acts in five TV programs for which he also co-writes the scripts. In New York and across Latin America, he can be seen in “La Familia Peluche” and “Vecinos” on the Univision network.

Derbez got his big film break in the U.S. market when he was cast opposite Kate del Castillo in the 2008 indie hit “Under the Same Moon.”

The son of Mexican TV and film actress Sylvia Derbez, he also appeared in “Blood of My Blood” (2007) and debuted on Broadway in 2005 in “Latinologues,” a collection of sketches about U.S. Latinos directed by Cheech Marin. He is a frequent host of the Latin Grammys.

These days, he’s filming “Anxiety,” a comedy with Eva Mendes. Later this year, he will be in Dennis Dugan‘s “Jack and Jill,” starring Adam SandlerKatie Holmes and Al Pacino.

Derbez has to thank Sandler’s domestic workers for the role. According to Derbez, the Hollywood funnyman was looking for a Latino actor and, unable to find one, he turned to his house staff, who suggested Derbez.

“Here I am paying to get agents in Los Angeles and trying to make good connections,” he says, “and look how I found this – directly and free.”