I remember a discussion about something like this a couple years back. From a purely technical standpoint, yes you make a religion to do with homestuck, as you can with anything, but I think a good point was made that tying your religion (something so intrinsic to your world view, morals, and in many cases lifestyle) to a piece of media in a capitalistic society opens you up to exploitation depending how you go about it. It is also a piece of media that can be rewritten, taken down, is tied to actual creators that you may or may not want the religion related to down the line.
I think if homestuck is spiritually important to someone to the extent of building a religion about it the only issue would be their safety and continued sanity (not saying that it’s an insane thing to do, but instead that due to previous points of being opened up to exploitation, they could be allowing for themself to be driven insane).
I’d recommend the person to actually sit down and essentially write their own scripture using the spiritually significant aspects in order to emancipate those aspects from Homestuck as media, and for their use as homestuck as religion