Having good indexes.
MySQL (or any other DB) should be able to handle millions of rows easily. The only things you need to think about is:
- how to abstract your data
- which fields to index
- and think ahead about what happens more: Read actions or Write actions (most apps have way more read then write actions)
When you have more read then write, you should make sure your data is written to the DB in a way that it's easy to get it out in the form you need it. Otherwise you'll be doing a lot of restructuring of data on every read action.
From this list, the abstraction and the indexes / foreign keys are the most important.
If your website gets bigger, you might also want to think about how the MySQL files are being handles (which partitions etc.) for the disk IO.
And if it gets even bigger, then you might want to switch away from MySQL to some distributed database solution.