Murray sprained his right ankle in the midweek win over the Southern Kings in Port Elizabeth and has been ruled out of the rest of the tour.
"Euan left the field because of the injury and has damaged the structures around the ankle joint. He is subject to further assessment, treatment and specialist opinion but may require surgical repair," said Lions Head Coach Ian McGeechan.
"The medical team have now fully assessed his injury and have determined that the injury is serious enough to mean he will play no further part on the tour. John Hayes will be a straight swap for Euan in the squad.
"John is an experienced international front row forward who has played 94 times for his country. He was an integral part of the Irish Grand Slam win this year and he also played four provincial matches on the 2005 tour to New Zealand and won a Lions Test cap against Argentina prior to the tour."
The Lions are hoping to get Hayes on a flight to South Africa this weekend, where he will meet up with the rest of the squad in Durban.
The other injury victim from the Southern Kings game, James Hook, continues to progress through the return to play protocol for a player returning from concussion. He is under continual monitoring by the Lions medical team.
Any decision on the date for his return to play will be made in due course.