United head to Huish Park as heavy favourites to see off the bottom side in England's third tier and progress to the next stage of a competition they last won in 2004.
However, Van Gaal has already seen his side suffer a sensational defeat to a League One side this season, when they were beaten 4-0 by MK Dons in the League Cup in August.
The vastly experienced Dutchman also pointed to cup shocks during his time at Ajax and Barcelona as he underlined the need for United to avoid complacency this weekend.
"We know from our early exit in the Capital One Cup that league places mean nothing in the cups, but I know that also from Ajax and Barcelona, so it’s not only like that in England," said Van Gaal.
"It is always a shock when you play against a lower team because you can assume that you have to win, but it is not like that in football.
"I have lost with Ajax against a lower team, against Cambuur for example. I lost at Barcelona against a third division team. I can't remember anymore - it has been wiped out of my mind. But we have lost."
Van Gaal acknowledges that the FA Cup could provide United, who sit nine points behind Chelsea and Manchester City in the Premier League, with their best chance of securing silverware this season.
"Yes, I think so. It is the shortest way to success, so you are right, we are very interested in the FA Cup and I think my players are also," he added.
"In the Netherlands, we have known for many years that the FA Cup is one of the most important competitions in football.
"The FA Cup was shown on the television over there at a time when it was not common to show matches from other countries."
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