Yamal was hurt while converting a penalty that secured an eighth-straight La Liga victory on Wednesday (Thursday AEST).
The 18-year-old and Portugal defender Cancelo, 27, had to be replaced with apparent muscle ailments that raise concerns ahead of the World Cup starting in June.
"Of course it's a real blow for us because Lamine is a very important player for the team," Barcelona midfielder Gavi said.
"He was upset in the locker room. I don't know how long he will be sidelined because of the injury, but hopefully he will be back as soon as possible because we need him."
Yamal converted his penalty in the 40th minute and immediately looked to the bench and signalled that he was hurt. He dropped to the ground as his teammates arrived to celebrate, then appeared to grab the back of his left leg.
The Spanish forward left the field on his own after being attended to by doctors and talked briefly with coach Hansi Flick before walking down the tunnel by himself.
Cancelo had already been replaced in the 24th for an apparent muscle injury to his right leg.
"We hope their injuries are not serious and they are back with us as soon as possible," Barcelona goalkeeper Joan Garcia said.
Elsewhere, fourth-placed Atletico Madrid's league struggles continued with a 3-2 loss at Elche.
Atletico have only one win from their last eight matches in all competitions and this defeat comes after losing the Copa del Rey final to Real Sociedad on penalties. Before that, Diego Simeone's team had eliminated Barcelona in the quarter-finals of the Champions League.
Andre Silva scored twice for hosts Elche, including the 75th-minute winner. He had already converted a first-half penalty, for which Thiago Almada was red carded.
Elche are out of the relegation zone with the victory, their third in four matches.
Sociedad's Copa celebrations were marred by a 1-0 loss to visiting Getafe, who moved up to sixth place with a seventh win in 10. Sociedad stay eighth with six rounds left.
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