He was tentatively set to face off in his debut against former UFC heavyweight champion Andrei Arlovski. He was then set to face Antonio Silva, however. The fight was soon called off as Silva was given a title shot against Alistair Overeem. Kharitonov next faced Tatsuya Mizuno at the year-end Dynamite show. He defeated Mizuno via a brutal knockout via a knee in the very first round.
He next debuted in Strikeforce against Arlovski in the first round of the Strikeforce heavyweight tournament. He defeated Arlovski via first-round knockout to advance to the semi-final round. He was expected to face the winner of the fight between Brett Rogers and a fellow Pride veteran in former UFC heavyweight champion Josh Barnett. Barnett was victorious and was set to face off against Kharitonov.
Barnett defeated Kharitonov via first round arm triangle choke.
Kharitonov was next rumored to face either former Pride heavyweight champion Fedor Emelianenko in M-1 Global or fight a rematch against Fedor's brother Aleksander Emelianenko. Instead, Kharitonov next signed to face Tony Lopez.
Kharitonov fought John Delgado instead winning via thirty-four second keylock submission.
- Sergei Kharitonov vs. Roman Savochka - Kharitonov came in undefeated. He won via TKO due to hand injury.
- Sergei Kharitonov vs. Murilo Rua - The fight is infamous for the unfortunate fact that Murilo Rua could very well have died inside the ring during the bout. He suffered brain damage. The fight was at heavyweight, whereas Rua fought normally as a middleweight or light-heavyweight. The fight was in the opening round of the Pride 2004 heavyweight grand prix. Kharitonov came into the fight undefeated.
- Sergei Kharitonov vs. Semmy Schilt - The fight was in the quarterfinals of the Pride 2004 heavyweight grand prix.
- Antonio Rodrigo Nogueira vs. Sergei Kharitonov - The fight was Kharitonov's first loss in his career. The fight was in the semifinals of the Pride 2004 heavyweight grand prix. Antonio Rodrigo Nogueira went on to a no-contest with Fedor Emelianenko later that night in the finals, with a headbutt cutting Fedor and postponing the final for four months.
- Sergei Kharitonov vs. Mu Bae Choi
- Sergei Kharitonov vs. Fabricio Werdum - The fight was Fabricio Werdum's first loss.
- Alistair Overeem vs. Sergei Kharitonov 1 - Kharitonov dislocated his shoulder badly early in the fight after an awkward fall but fought through it.
- Aleksander Emelianenko vs. Sergei Kharitonov - The fight was Aleksander Emelianenko's final fight competing for Pride.
- Alistair Overeem vs. Sergei Kharitonov 2 - The fight was in K-1 HERO'S.
- Sergei Kharitonov vs. Jimmy Ambriz
- Sergei Kharitonov vs. Jeff Monson - The fight was the first time that Kharitonov had been submitted in his career.
- Sergei Kharitonov vs. Tatsuya Mizuno
- Sergei Kharitonov vs. Andrei Arlovski - The fight was in the quarterfinals of the Strikeforce heavyweight tournament, and it was Kharitonov's Strikeforce debut.
- Josh Barnett vs. Sergei Kharitonov - The fight was in the semifinals of the Strikeforce heavyweight grand prix.