Dean gets rid of the Mark of Cain in Season 10, Episode 12, “About a Boy.” A spell turns him into a 14-year-old, and the Mark disappears while he’s changed.

Quick note

The Mark later returns when Dean becomes an adult again, so that episode is the temporary removal, not a permanent cure.

Extra context

If you meant the first time Dean’s Mark is fully dealt with in the storyline, that comes much later in Season 10, Episode 23, “Brother’s Keeper.”