The MADS box-containing transcription factors MEF2A-D regulate the expression of most skeletal and cardiac muscle structural genes. Recently, a zinc finger protein called HZF1 was identified as a transcription factor, and found to be highly expressed in cardiac muscle. By screening the transcription regulatory region of HZF1, we found that myocyte enhancer factor 2 (MEF2) potentially recognizes and binds the regulatory region of the HZF1 gene. We also found that the knockdown of MEF2A endogenous expression in human aortic smooth muscle cells decreases the expression of HZF1, while the enforced expression of MEF2A in turn promotes the expression of HZF1. Furthermore, we employed the luciferase reporter system and chromatin immunoprecipitation (ChIP) to demonstrate that MEF2A does in fact bind the regulatory region of HZF1, which suggests that HZF1 is the direct target of MEF2A. Based on the fact that MEF2 proteins function as essential regulators of cardiac development and as important pathological factors for certain cardiac diseases, our finding that MEF2 positively regulates the expression of HZF1 may contribute to further research investigating the role of the zinc finger protein HZF1 in cardiac development and disease.