What are you trying to do with your data? I use even larger data sets than that all the time, and Excel seems to lock up all the time. However, when I pull up task manager, I see that the CPU is just maxed out. Give it time, and eventually it finishes its calculations.
To avoid frequent re-calculation on the data, turn off auto-calculation (Tools -> Options, Calculation tab, set calculation to manual).
If you have a lot of formulas in the data, try replacing the formulas with their actual values so your sheet does not have to constantly re-calculate. After it has finished calculating once, just highlight all the formulas and hit CTRL-C, then Edit -> Paste Special, select Values, and hit OK. If you have some valuable formulas in there, make sure you store those in some other place before doing this.
Does that fix your problem?