Twist-related protein 1 (Twist1), also known as class A basic helix-loop-helix protein 38 (bHLHa38), has been implicated in cell lineage determination and differentiation. Previous studies demonstrate that Twist1 expression is up-regulated in gastric cancer with poor clinical outcomes. Besides, Twist1 is suggested to be involved in progression of human gastric cancer. However, its biological functions remain largely unexplored. In the present study, we show that Twist 1 overexpression leads to a significant up-regulation of FoxM1, which plays a key role in cell cycle progression in gastric cancer cells. In contrast, knockdown of Twist 1 reduces FoxM1 expression, suggesting that FoxM1 might be a direct transcriptional target of Twist 1. At the molecular level, we further reveal that Twist 1 could bind to the promoter region of FoxM1, and subsequently recruit p300 to induce FoxM1 mRNA transcription. Therefore, our results uncover a previous unknown Twist 1/FoxM1 regulatory pathway, which may help to understand the mechanisms of gastric cancer proliferation.