The Arsenal midfielder impressed during the Three Lions' 2-2 draw with Ecuador in Miami on Wednesday, but was forced from the field after 63 minutes following a challenge from Carlos Gruezo.
Oxlade-Chamberlain's ankle was caught by the South American midfielder, but it was the way in which he landed on his knee that caused his withdrawl - and Hodgson admits the 20-year-old faces an anxious wait to discover whether he has sustained what could be a serious injury.
"We have our fears there might be some ligament damage," Hodgson told reporters.
"Oxlade-Chamberlain is the one that bothers. His knee buckled under the challenge as the player turned into him. He'll have a scan tomorrow, I'd imagine. When we've had the scan, we'll know more.
"My hope is that Oxlade-Chamberlain will not be seriously injured. He did every so well tonight and looked really, really sharp.
"It would be an enormous blow if we were to lose him, so I'd prefer to concentrate on the satisfaction and positivity I can take from the game."
The Emirates starlet has only just recovered from a groin injury that saw him miss the end of the Gunners' Premier League season, and will be sent for the scan on Thursday prior to England's final pre-World Cup friendly against Honduras on Saturday.