The transcriptional factor Yin Yang 1 (YY1) plays multifunctional role in various biological processes. Here we report that the silencing of YY1 using siRNA expression vectors in U2OS cells led to a significant decrease in transcriptional activity of p73, which is a member of p53 family. Consistently, overexpression of YY1 could enhance the transcriptional activity of p73 in a dose-dependent manner. Moreover, synergistic cooperation between YY1 and E2F1, through a mechanism involving a physical interaction, was observed in the regulation of p73 promoter. In conclusion, our results provide new insights into the function of YY1, and might clarify the complex regulation mechanism by YY1 network in diverse biological processed, such as development, differentiation and cancer biology.