I bought a Europa spezial ticket from Berlin to Prague. The train's final destination is Praha hlavní nádraží, the train stops enroute at Praha Holesovice, can I get off at Praha Holesovice without this causing a problem?

Certainly. So long as you don't travel beyond your destination station, you can get off wherever you wish.

I am afraid TimS is wrong. Europa Spezial means you can only use the connection as booked. This means, no interruption. Of course, you can leave at Holesovice, but for the ride from there to Praha hlavní nádraží you need a new ticket (which won't break the bank).

I would assume that justshootme doesn't intend to go the rest of the way. Perhaps that station is closer to where he(she) wants to be.

Kristinelaine is correct. I would rather get off at Praha Holesovice if this doesn't cause any problems, I do not intend to use the remainder of the ticket.

Of course you can get off before - how are they supposed to know when you are not on the train?
You just cannot get on again, at least not without risking a fine.

"Of course you can get off before - how are they supposed to know when you are not on the train?"

Actually sometimes it is not as easy as this as tickets are inspected at the train station when leaving (especially in Britain). I don't know if this is done in Prague so I can't advice the op.

I have not seen them inspected on leaving the train anyplace else than the UK. You can certainly get off at the earlier Prague station rather than take the train past your hotel to the main station and then have to back track. We did it an had no problem at all. And there were plenty of taxis at the station even though we arrived late in the evening.

I live in the Czech Republic and can confirm that tickets are not inspected when you leave the train.