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I have an old socket 775 motherboard, currently running DDR2-667 PC3-5400 chips.

I want to rip them out and replace them with 2x2GB PC2-5300 blocks, but the manufacturer's QVL for memory does not note these as "compatible".

Will I run into any issues regarding the chips?

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DDR2 -667 PC3 -5400 ??? Just to note - or DDR-II (synonym of PC2) or PC3 (synonym of DDR-III) –  Lazy Badger Nov 15 '11 at 17:29

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No you probably can't.

While both PC2 and PC3 memory uses a 240-pin connector, they are keyed differently so they'll only fit in board designed specifically for their type. The notch in the memory chip connector edge will prevent you from connecting the incorrect memory.

If your old board supports PC2, PC2 is all you'll be able to put in it.

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Most probably - no, memory is freely (to some extent) exchangeable.

Just note: there can be some special pre-reqs for memory (non-standard Volts for memory, only some allowed timings), which you must follow

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Memory is not freely interchangeable. You must replace memory types with the same memory types. You can change density to an extent (depending on controller compatibility) and you can change speeds, but PC2 can only be replaced with PC2, and PC3 can only be swapped out with PC3. –  music2myear Nov 15 '11 at 17:08
    
I mis-read question, yes. DDR-II|DDR-III is more familiar notation for me than PC2|PC3, and while OP noted DDR2 only once, I assumed that both are the same type. Mea culpa! And note - memory mentioned as 5300-5400, which (as 5300) exist only as DDR-II, DDR-III started from 6400. –  Lazy Badger Nov 15 '11 at 17:36

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