As an instance admin, it’s possible to defederate with an instance, in which case posts and comments by users of that instance will no longer replicate to your instance.

As a regular Lemmy user, there is no instance-level block. You can instead:

• Block individual users as you encounter them. Maybe the whole instance isn’t a problem and blocking a dozen folks is enough.
• Block a community. If I understand it correctly, this is not the same as blocking every user in the community. It just unsubs you and prevents the posts from showing up in all for you. Users that participate in the community could still interact with you in OTHER communities though.
• Abandon your current account and join (or create) an instance that blocks the instance you don’t like. Your post and comment history would stay with your old account, users that knew you under your old account might not be able to find your new one unless you leave a goodbye post or update your profile… though Lemmy is still small enough that if you’re active and use a similar user-name on the new instance they’ll probably recognize you.