My dad had an '02 GMC Sierra Denali with 6.0 liter that has been getting a random misfire code. Sometimes it flashes the SES light while driving.
So far the fuel and air filters and spark plugs were changed and the MAF was cleaned.
Is there a common cause for this or is it going to be a lot of parts replacing?
Also, it sounds like it might have a small exhaust leak. Can that possibly cause the misfire?

Check for vacume leaks around the throttle body gasket and intake area. Intakes have been known to leak at the gaskets. Check for a restriction in the exhaust (plugged cats, or muffler) and it might be time for an injector flush.

How do you find vacuum leaks and exhaust restriction? Do you need special tools? Is an injector flush something that has to be done at a dealer or is it something that can be done myself?

Get a can of spray carb cleaner and spray gasket areas while the engine is running, if the engine starts to stumble, you have a leak. Do NOT get it close to the exhaust areas or flame-age might occure.

An exhaust shop should be able to tell you if you have a plugged exhaust system or if the truck has no accelleration above 45mph or worse yet, full throttle gets you no where, you might have an exhaust problem.

Find a BG Products dealer near you and let them flush the entire fuel system.

Check for vacume leaks around the throttle body gasket and intake area. Intakes have been known to leak at the gaskets. Check for a restriction in the exhaust (plugged cats, or muffler) and it might be time for an injector flush.

X2 my 02 yukon was getting the same code,it was a intake leak

you should get an injector flow test done that will tell you if is an injector and if one or more are plugged you will need to remove the fuel rail to see if rust is getting in there. I have seen a lot of the 6.0's with rust in there either from the fuel lines rusting from inside or really crappy fuel. you used ac delco plugs right??? most others are junk.

My brother changed the spark plugs. I am pretty sure he used AC Delco iridium plugs.
Thanks for all the suggestions. Hopefully they will take care of it.