The Manchester City midfielder is now a doubt for his club's trip to West Brom on Saturday, with Santi Cazorla of Arsenal coming on for him after just 13 minutes
The attacking midfielder started alongside Pedro and Cesc Fabregas furthest forward for La Furia Roja, but minutes after teammate Sergio Busquets was clattered by Patrice Evra, Silva looked to be struggling.
After a few moments of attempting to run off the knock, Silva was forced to leave the pitch, clutching his hamstring before heading straight for the tunnel at the Vicente Calderon in Madrid. Arsenal's Santi Cazorla replaced him.
The former Valencia star is now a doubt for City's tough upcoming Premier League match on Saturday when the Premier League club facers West Brom at the Hawthorns, with Steve Clarke's men yet to drop points at home so far this season.