Yes, it can. And what are you using at the moment?

If you are looking to upload huge file as a whole at once, than you are out of luck, browsers and various add-on technologies that we use to patch features that are not yet present in browsers, are yet too far from adequate state. So the only way for you to get consistent upload for large files would be to enable chunking. Plupload supports that out of the box.

We've tested files up to 8.93gb, with html5 runtime in Chrome, Opera, Firefox and IE10 (basically any browser that supports File.slice and XHR Level 2 should work). So if you plan to work with html5 only (that's what jQueryUpload uses anyway), then your answer is - yes.

Talking about other runtimes, Flash definitely can upload files larger than 2gb (but - with no chunking enabled - that is a paradox, but that's how Flash works, they do not directly let you manipulate internals). Officially Adobe supports only files up to 100mb, anything that is beyond is not guaranteed. It might easily die somewhere in the middle, with no way to resume.

SilverLight can upload files larger than 2gb with enabled chunking (we had a successful test with 7gb+ file).

And then there's a Java runtime in the wild that basically supports any size.

Where do you plan to use Plupload? Recently we've rewrote Plupload Core from scratch and potentially opened ability to retry failed chunks, encode and checksum them, etc. Would be really interesting to try it in a stressed real world scenario.