Gene expression in myogenesis is governed by multiple myogenic factors including MyoD. Previously, we demonstrated that TBP-interacting protein 120B (TIP120B) promotes in vitro myogenesis through its anti-ubiquitination ability. In this study, we investigated interplay between MyoD and TIP120B. Mouse C2C12 cells subjected to myotube differentiation contained increased amounts of TIP120B and MyoD. Dexamethasone, which inhibits myogenic signaling, decreased the amounts of those proteins. Mouse and human TIP120B promoters, which carry multiple E-box motifs, were potentiated by MyoD. In the human TIP120B, a proximal E-box binds to MyoD in vitro and exhibits MyoD-dependent transcription activation function. Expression of the endogenous TIP120B gene was correlated with the level of MyoD in different types of muscle-related cells. Furthermore, MyoD binds specifically to a proximal E-box-carrying promoter region in chromatin. Proteasome-sensitive MyoD was increased and decreased by overexpression and knockdown of TIP120B, respectively. Moreover, stability of MyoD was increased by TIP120B. The results suggest that MyoD and TIP120B potentiate each other at gene expression and post-translation levels, respectively, which may promote myogenesis cooperatively.