Yes, DIFFERENCE is a Scrabble word!

Letter values in Scrabble US: D 2, I 1, F 4, F 4, E 1, R 1, E 1, N 1, C 3, E 1.

Is it a valid word?

DIFFERENCE is a valid word in the official Scrabble dictionary (US), the UK Scrabble Dictionary and Words with Friends (ENABLE).

the quality of being unlike or dissimilar
a variation that deviates from the standard or norm
a disagreement or argument about something important
a significant change
the number that remains after subtraction; the number that when added to the subtrahend gives the minuend

Also: difference of opinion.