Marketing Cloud uses Microsoft SQL Server which has a row limit of 8,060 bytes. Columns that don't fit are placed off-row, in a separate internal table and when you run a query on the Data Extension, the platform has to execute multiple queries, which can result in a time-out.
What you can definitely do, is reduce the number of columns and make sure you don't have unnecessary overhead when it comes to field length. Also only import the data you need and always assign primary keys or composite keys.
If would be beneficial if you could provide the Data Extension structure and the query that you are trying to run.
You can read more about query best practices here: Optimize SQL Query Activity performance in Marketing Cloud