Context for my answer: I am what I call "confusedidextrous" - I do some things left-handed (like most knife use) and some things right-handed. 5/8s of my great-grandparents were lefty. I have big hands and used to be a musician, so I have a good bit of finger strength and dexterity. Anyway...my answer to you based on my experience.
For me, it all depends. First, I find framelocks easier than linerlocks in most cases, with either hand. The locking leaf is usually bigger and thicker. Second, I hate to say this, but with liner locks, it all depends on the specific design. Linerlocks with litte or no cutout like the Spyderco Khukuri, are tough with either hand. I find the Spyderco Military easy with my RH but hard with my LH due to the shape of the grip. OTOH I find Emerson liner locks much easier with the LH and difficult with the RH, and haven't really been able to figure out why.
So my recommendation is, if at all possible, try the specific knife first. I avoided liner locks for years and years but have been recently trying them out and found quite a few that work for me BETTER as right hand models than in left hand models.