I guess it depends. The easiest thing would be making it inconvenient to get in the room for no perceived reward. Maybe it's a known room but everyone thinks it's empty/unimportant and it's blocked by an obstacle (boulder, waterlogged door, etc).
If you're going to introduce higher technology or magic, then a lock would make the most sense. Maybe it's opened by someone or it could even be a time or situational lock.
If there's high incentive to get into the room, then there's a couple options. You could make people believe they already accessed the room when the real room is hidden. It could be impossible to enter - no door, difficult material, catastrophic event that moved/blocked it, or even everyone knew of the room but doesn't know where it is now. You could make social deterrents. Maybe there's a superstition around the room, a religious indictment, security personnel, etc.