delete the music from your computer and iTunes will not be able to find it.
If iTunes cannot find it, it will not be in the playlist for the iPod and will be removed from the at the next sync.
In iTunes, go to File > Library > Organize Library > Consolidate files.
This will copy all your music tracks into the iTunes library so that you will be able to delete any music file that is external to the iTunes library without a problem.
P
To make room on my HD, I wanted to delete some music files that I'd already put into iTunes & my iPod. If I were to do that, would it effect my iTunes library?

Chowhound
Comic Vine
GameFAQs
GameSpot
Giant Bomb
TechRepublic