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So, to start off, grenades are completely useless for this boss. Salazar's entire gimmick is that he's protected by an impenetrable outer shell, and you can only damage Salazar himself when it opens (this you kind of see during the initial cutscene).
The best/safest strategy is to play defensively; let him do an attack first, dodge it, and then fire back while his shell is still open. Easier said than done, but I'm happy to list his main attacks so you know what to watch out for.
For most of the fight, he'll swing around the room at a distance and fire off acid blasts. These can be either horizontal or vertical. Crouch (the dodge button) whenever you see a horizontal blast coming your way, and if he starts spitting down a vertical blast from above, run like hell--it moves and you don't want to get caught up in that. The third kind is a barrage sort of attack that can really hurt; always use the pillars to duck behind cover when you feel you need to.
Dodge the acid blast, and you then get a chance to snipe or handgun-shoot him from afar.
For his instant-death move, he'll crush Leon to death in his "jaws." Thankfully, this is easy to predict, since Salazar will slowly creep into your melee range before doing it. Just dodge this by running away, and then Salazar is already close enough that you can just shotgun blast him in the face.
After enough damage, Salazar will be momentarily stunned--he'll actually fall off the wall if he was currently "airborne" at the time. This will allow you to run up and do a special knife move for big damage.
Other than that, definitely shoot any of the acid bubbles he drops on the ground--they explode if you run into them and you don't want that happening.
Otherwise, the name of the game is patience and stay on the move. Play defensively; let Salazar attack first, evade, then strike back when you see that opening.
Basically what Darkgamester had said.
Throughout the Ramon Salazar boss fight, look around the area and look out for the acid bomb trap. Disable them as you run around with any gun shot. Touching these bomb will damage you, but disabling them award you one rng drop, usually handgun ammo. Due to the enormous amount of handgun ammo drop per disabled acid bomb trap, you can tackle this boss fight with handgun weapon solely without worry of running out of ammo, including with the Matilda.
It may take several tries to figure out the boss attack patterns, but you will eventually able to do it.
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The renowned golden egg method.
There are two golden eggs throughout the game, one in chapter 4 chicken farm accessible with boat.
The other one in chapter 12, after defeat Krauser, return to the throne room which is located after the duo Garradors room, in the throne room, there will be one gimmick lock box, opening it will reveal the golden egg.
https://steamcommunity.com/sharedfiles/filedetails/?id=3162561374