"Since the World Cup, my mother has been taken to hospital twice and my responsibility is to take care of her," Riquelme was quoted as saying by Villarreal's official website.
"It was an easy decision to make. My family comes before the football," the 28-year-old added.
Riquelme, who joined Villarreal permanently in 2005 after failing to hold down a regular place at Barcelona, played 37 matches in his nine-year spell with Argentina.
He was left out of his country's squad in the 2002 World Cup but returned four years later under the guidance of coach Jose Pekerman.
Despite their strong start, Argentina were knocked-out from the quarter-finals at the hands of hosts Germany.
Riquelme said that despite his decision, he will miss the Argentina jersey.
"It will hurt me deeply not to wear the Argentina shirt again but my mother's health comes first," he said.
"There's been a lot of bad blood and I don't want to make her suffer. My mother is my mother and I can't compare her with the Argentina shirt or anything else."
The former Boca Juniors player last featured for Argentina in their 3-0 defeat to Brazil in a friendly at Arsenal's venue Emirates. He was even named captain of the Argentinean team.
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