My page is divided into 3 frames. If I modify a css file used in one of the frame. After ctrl-F5 refresh the main page, it won't force reload that css file. Is this the way how frameset works? Is there any way to resolve this? Please advise, thanks.
Caching behavior is a function of the browser, so there's no real "standard" for forcing the browser to reload resources. It's not something that's defined as part of a frameset, so things may differ browser to browser and version to version.
Most browsers have the option to reload all resources by Shift-Refreshing (or Ctrl-F5 as you mentioned), but that may only work for the main page, and not individual frames. Try right clicking on the frame you want to reload, holding Shift, and choosing the menu item for the refreshing the frame (in Chrome it's "Reload Frame").
Also, look at this question/answer for an explanation of the Refresh behaviors of different browsers.