The most likely cause of this as some process that is generating large numbers of swap files. These are invisible to the Finder, but can lock down tremendous amounts of disk space. Download OmniDiskSweeper (an application that that checks disk usage) and check to see if that's the problem; swap files will show up in that app, and you should see a big block of them. If that's the case, open Activity Monitor (/Applications/Utilities/Activity Monitor.app) and see if there's a process with a very large memory or virtual memory footprint. quitting that app will release the swaps and free up memory, but you'll need a longer term solution if it's something you need to have running.