Played on Easy difficulty.
It all started when I wanted to kill Nihilanth faster than the old usual way done in Half-Life speedruns, which was a 40-45 second kill.
I started to use the Gluon Gun to immediately begin damaging Nihilanth as soon as possible as well as using the Gauss-rifle to shoot him and two of the crystals at the same time. I got the kill down to 34 seconds at best but 36-38 second on average. This was on Hard difficulty.
I later began playing on Easy difficulty and I wanted to optimize the kill for this difficulty. The difference between Easy and Hard difficulty on Nihilanth is that he has 200 less hp on Easy (800 total). There is ~1.2s delay before you can damage Nihilanth (you're stuck in a black space from where you get teleported into the boss room) so I used this spare time to cook a grenade which I throw as soon as I can for it to do damage. This way got me down to 30 seconds at best but it varied a lot, most often between 33-38 seconds.
I wondered what caused this huge time difference even though I did pretty much the same thing every time so I studied the segmented run, HL21, a bit closer and noticed that Nihilanth doesn't do any attacks. So I thought when Nihilanth's head is opened depends on what he's currently doing and if he doesn't do any attacking, his head will open sooner (I noticed this using Notarget once but didn't think much of it at the time).
I started to use the last Gauss-rifle charge for the last crystal to also damage Nihilanth at the same time. I started to get low 30's more often. Then, I remembered from the segmented crowbar only run how you could move in a certain way to make Nihilanth unable to attack you. I tried it out and I got him to open his head at 25 seconds. Being more prepared for such an early opening this time I grenade boosted up to be able to deal the final blow. Now getting a sub 30s Nihilanth is ez pz.
In my opinion a very easy strat when you get the hang of it. It also shouldn't be very different at all for Hard difficulty. Although this strat to me seems pretty optimized, I imagine there are more efficient ways in dealing sufficient amounts of damage.
The goal is to deal 800 damage as soon as possible to trigger some sort of timer for Nihilanth's head to open and make sure Nihilanth doesn't do anything that keeps the head from opening. The current position of Nihilanth and his looking direction could possible also have a role in the outcome. The first few seconds is done blind as when entering the map the screen is black and fading in, but this is not visable as this is a recording of a demo and demos doesn't show this fade in from black.
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