No. You can build lineups without one. But nearly everything SaberSim does beyond building depends on it.
An entries file tells SaberSim which contests you're playing. With it:
Contest Sims know the exact size, fee, and payouts of each contest you entered.
The Portfolio Diversifier builds a set of lineups diversified for your specific contests.
Lineup groups fill your contests, and your lineups can be saved and uploaded to the DFS site in a couple of clicks.
Quick Swap and Full Swap know which lineups to swap.
Without one, you get a Lineup Pool and can make a lineup group by hand, but nothing is matched to a contest and there's no file to upload to the site.
Register for your contests first, download the entries file from your site, and upload it.
A placeholder lineup in each entry is fine. SaberSim overwrites it when you build and save your lineups.