Running Game which has no ISO file in the disk.

[Ryudo]

I have made tons of ISOs myself, including some very recently with the latest builds and the issue still doesn't happen.

I've even tried forcing PCSX2 to close while it's using an ISO to see if it causes any kind of corruption, but again nothing happened.
The most I've had happen with PCSX2 is memory card corruption, but that happens even on the regular PS2.

Can I ask what software you used to create the ISOs that ended up being corrupt eventually?

[Blyss Sarania]

PCSX2 doesn't open the ISO for writing, so this can't be PCSX2s fault. Also as stated, if this was a thing then we'd have tons of (rightfully) angry users beating down our forum every day in anger. I've only seen reports like this 3 times(counting this one) in the two years I've been a mod. Both of the previous times turned out to be user error - one guy had a bad HDD, another guy was opening his ISO in a hex editor and that was what was doing it.

Either way - The question Ryudo asked is a good place to start. Also run a software like HdTune or anything that can read SMART and check your HDD health might be good. Big files like PS2 ISOs will tend to reveal HDD problems earlier than small normal files because they take up more physical space on the disk so there is more of a chance they will encounter a bad spot.