Hello,
A few things to check: make sure you are not running third party antivirus software (Bitdefender, Malwarebytes, Norton, etc.) as they can sometimes prevent Mach4 from accessing necessary file. Likewise, you need to run Mach4 as an administrator. To do that, right-click on the shortcut and go to Properties, then Advanced, then select 'Run As Administrator' (if you're using XP the steps are a bit different, but that's the general idea). Next, make sure Mach4 is run from your C: Drive and is called Mach4Hobby. If it's somewhere else or the name of the directory was changed, that can cause issues like what you're seeing. One last thing to check is that your motion controller is connected. I am not very familiar with the one you're using (have not used it personally and only tested it a handful of times) but some motion controllers need to install firmware updates once connected in order to use them. One example of that is the UC100. I hope one of these helps!
-Bryanna