Michael Clarke Duncan was originally intended to play Ben King, reprising the role from the first game. He passed away very early into the voice recording process, however, and the role was recasted to Terry Crews. At one point during the credits, however, there is a moment where the entire voice cast sings along to Biz Markie's "Just a Friend." Duncan had completed the recording for that part and thus is heard along with the rest of the cast as a tribute. Towards the end of the song, the various cast members' voices all fade out, leaving only his voice to finish the song.

Scenes between Roddy Piper and Keith David make references to their appearance and very realistic fight from "They Live". Piper appears as a manifestation of of David's nightmares over the shoot.

Enter the Dominatrix was originally one of the downloadable content for Saints Row: The Third. However, due to time constraints and THQ, the publisher of Saints Row game series, went bankrupt, Volition Inc. decided to merge it with Saints Row IV.

In gameplay, the player can be heard saying sometimes after killing someone, "I am the one who knocks!" This is a reference to Walter White's quote in Breaking Bad (2008).

The name of the mission "Nytefall" is a reference to Batman comic storyline "Knightfall" wherein Batman is temporarily crippled by Bane and has someone else fill in for him.

Some of your homies super costumes are plays on other video game and movie characters. Pierces costume resembles Kung Lao from the Mortal Kombat franchise. Kenzie's costume is Raven from DC comics and more known from Teen Titans. Ben King is Morpheus from The Matrix franchise

In one of the later missions, Johnny Gat says "You think I'd wanna go to Hawaii? Hell no!" Daniel Dae-Kim, who voices Gat, plays Chin Ho Kelly on the CBS television show, Hawaii Five-O.

The title of the DLC "How the Saints Save Christmas"is an allusion to the Dr. Seuss' book How the Grinch Stole Christmas.

Post credits of one of the alternate endings(in which all loyalty missions were completed) it is revealed that the Narrator has all along been author Jane Austen who was kidnapped by Zinyak via time machine.