It uses a d6 instead of d20, 5e's advantage/disadvantage mechanics, and close to 0 numeric modifiers. There are degrees of success instead of pass/fail.
Separating the role/class combinations let them pack a lot of possible concepts and fighting styles into one smaller package.
There's also a bunch of minor rules changes for combat, like Marks not overriding each other but stacking, opportunities hitting automatically, slows disabling shifting, etc. Numbers are a lot lower, with the average attack doing 2 damage, a character having 10HP for its entire career (unless he decides to tank it up).
Feats are a lot more meaningful, none of that sitational bonuses crap.
On the skills side, it doesn't have a set skill list (players are either supposed to make up their own, or have the GM make a list), and it also utilizes Tricks and Complications, which were nabbed from Fate I think; playing out complications nets you Action Points which you can use for your Tricks.
There's also many optional systems to expand on the simple core rules, like Kits (gives a sort of "theme" for your character that gets him flavor based abilities) Team Conflicts (a bit abstract alternative to a 4e skill challenge), Chases, stuff like that.
What it doesn't have at the moment is a real equipment system. I heard it's in the works, but the dev had to put it on the back burner because of personal problems. Also, the layout is a mess.
If you are happy with how 4e plays there's a chance you'll find Strike! a bit too stripped down. It lacks the massive amount of content and built in flavor 4e has, and just doesn't bring the same sort of "numbers go up" thrill. There's also noticably less charop/character building puzzle.
If those sound like positives, you should give it a try. If they sound like negatives... still give it a read at least, maybe you'll find something you like.