"They did the right thing, Asriel. They did." - Chara, at the end of the Genocide RunThe Genocide Run, much like in the original Undertale, is where Frisk kills all the monsters. However, unlike the original, it plays differently, depending on whether you either spared Flowey or not.
Flowey is spared Edit
After sparing Flowey at the beginning, Frisk goes on to slaughter all the monsters, including Toriel, who begged for mercy. While Flowey still tells Frisk to fight in the Ravaged Mines, he didn't encourage Toriel's death after she begged for her life. When Frisk kills Toriel, their LV increases, not knowing the dangers that will be foreshadowed.
Sans is oddly much more friendly to Frisk than in the Pacifist Run, calling them "his best pal". However, as Frisk progresses past Tundra Town, and even while Papyrus bullies Sans, Sans warns Frisk to stay away from Papyrus at all costs. When Papyrus dies, Flowey becomes even more hesitant of trusting Frisk, and Sans disappears.
At the Wasteland, Frisk attempts to kill Monster Kid, which Flowey outright yells at Frisk for doing, and attempts to stop them from doing so. When Frisk does kill Monster Kid, Undyne rushes in at the last second to stop them, only to be wounded in the process. This causes them to rise from the ashes, and becomes "The Undying Demon", and tries to kill Frisk. However, she dies, and Frisk and Flowey move forward to Hotland.
In Hotland, Mettaton immediately identifies Frisk as a threat and attempts to kill them right there and then. However, Alphys disables Mettaton and befriends Frisk, as the two are equally insane. Alphys guides Frisk through Hotland and the Core as they slaughter innocent monsters together. All of this ends at the Core Elevator, where Alphys learns that Frisk killed Undyne. Alphys reboots Mettaton and combines him with the Amalgamates, transforming him into MTT NEO. Flowey runs away, but Frisk doesn't. They kill the robot and Alphys, steal the vials of determination in her coat pocket, and head to New Home.
Frisk reaches the Judgement Hall and sees Sans staring at them. The battle initiates, with it being significantly harder than during the Pacifist Run, and only ends after 50 turns when Asgore intervenes and kills Sans from behind, calling him a "waste of dust". Asgore tries to finish off Frisk himself, but fails. Flowey returns and absorbs the 6 Human SOULs, transforming himself into Alpha Flowey, however, unlike in Undertale, where Flowey toyed with Frisk. Flowey does everything in his power to kill Frisk.
Frisk defeats him, and Flowey, almost dead, absorbs all the remaining monster souls from the Underground and becomes Asriel. Asriel once again tries to defeat them; however Frisk, with all the Determination they took from Alphys' corpse, defeat the "God of Eternal Life". After the fight, Asriel shows his true colors, and tells Frisk that they "didn't want to let these monsters live", and wanted to have a better life in the surface. He tries to stop them, but Chara intervenes, and tells Asriel that "everything is now at peace" now that the monsters have been destroyed. Asriel now accepts his fate, and, with his last remaining power, destroys the barrier, and lets Frisk be free, getting their happy ending.
Flowey is killed Edit
After killing Flowey, Frisk goes on a slaughtering spree to kill all the monsters, including Toriel, who begs for mercy. Everything is still the same in this route, but with one difference.
After the battle with Asgore, Sans rushes forward and kills Asgore and absorbs the 6 Human SOULs, transforming himself into Omega Sans. After Frisk defeats Omega Sans, he breaks down and tells Frisk that "they have a chance in this world", and gives the option to either Kill him, or Spare him. If Spared, he kills Frisk, mocking them on how gullible they are. If Killed, they give out these final words:
"you really do hate me, do you?"
Sans self destructs, breaking the barrier in the process, giving Frisk their happy ending.