"Your last attack deals 2 times more critical damage."
Synergies
The Hunter's Grenade can be used to artificially elite enemies if the player can still extract a blueprint from the enemy, which will enable the crit condition. Slaying the artificial elite will drop the previously used Hunter's Grenade, allowing for an endless cycle.
Tainted Flask can be used in conjunction with the Hunter's Grenade.
Notes
The base critical DPS of Giantkiller is the third highest in the whole game, with the first highest damage dealing item being Scythe Claw.
However, to truly take advantage of Giantkiller's very high damage, the player needs to land the third and fourth hit of the attack combo, which puts them at risk of getting hit due to their slow wind-up. Therefore, using Giantkiller against normal enemies is relatively inefficient compared to other gear (even the Broadsword can easily take its place) but extremely strong against Bosses and Elites.
The Giantkiller is the only single-slot weapon in the entire game that cannot be stored in the backpack.
This is for balancing reasons to prevent the player from easily defeating bosses while still being able to wreak havoc on normal enemies.
This can be partially circumvented by dropping the Giantkiller and replacing it with the other desired weapon for the level before returning and equipping it while placing the other weapon in the backpack.
The Cursed Sword, by contrast, needs no such limitation since the core tradeoff of that weapon (very high damage and fast attack rate, at the cost of being cursed) isn't compromised by the backpack mechanic: the curse downside still applies even when the weapon is stored away.
Trivia
When this weapon was originally introduced, it was only available through the Daily Run. It was impossible to unlock the Giantkiller under normal gameplay and was thus only obtainable through modding.
The Giantkiller may have initially been conceived as a spear, like the one originally used to "kill" the Giant, but was changed to a sword at some point before being added to the game files.
The in-game model for the Giantkiller appears to be a sword with a long, straight-edged blade, with a white glow. This model is currently also used for the Seismic Strike.
The flavor text is a reference to the phrase "The bigger they are, the harder they fall".