A friend of mine flipping houses. She is running low on cash and does not have enough credit to help. She is asking to borrow money from me to help them finish the house so they can sell it. In return I am being offered a great return on my money when they sell. However, I still need to protect myself. Can I file a lien on the house to make sure I am paid at closing?

You need to loan the money as a mortgage, and have it use the property so it would be a lien filed on record against the property.

If they flip houses, and make such a return on the sell, why are they short of money?
Why can't they merely get a loan ?
But the only way I would let them have the money. Not all flips work as planned, many do but not all.