【Objective】To explore the correlation of dopamine receptor 4（DRD4）expression with clinicopathological characteristics and the prognostic significance after examining the expression of DRD4 in hepatocellular carcinoma（HCC）and non-tumor tissues；to show the effect of DRD4 agonist PD-168077 and inhibitor L-745870 on proliferation， migration and invasion of HCC cells， and to reveal its possible mechanism.【Methods】Immunohistochemistry and real time qPCR were implemented to detect the expression of DRD4 protein and mRNA in tumor and non-tumor tissues and prognostic significance of DRD4 expression was analyzed. To reveal the impact of PD- 168077 and L- 745870 on HCC cells，CCK8 and Transwell were performed；the signaling pathway was monitored by Western blot，and was verified with a specific inhibitor.【Results】Eighty-five（43.4%）of 196 HCC tissues had high expression of DRD4 protein；non-tumor tissueshad higher expression of DRD4 mRNA in 74 pairs tissues，and DRD4 mRNA was highly expressed in non-tumor cell line Miha compared with HCC cell lines. Patients with high DRD4 expression significantly had longer recurrence free survival（RFS）and overall survival（OS），and DRD4 was an independent prognostic factor for RFS and OS in patients after HCC resection（P<0.05）. PD-168077 showed a dose-dependent inhibition on proliferation，migration and invasion of HCC cells（P<0.05），while 1nmol/L of L-745870 significantly enhanced the proliferation，migration and invasion of HCC cells（P<0.05）. PD-168077 inhibited the phosphorylation of ERK，while L-745870 promoted the phosphorylation of ERK. The ERK inhibitor PD98059 could reverse the effect of L-745870.【Conclusions】HCC patients with high DRD4 expression had better prognosis and DRD4 might be a biomarker for prognosis of HCC patients. DRD4 might become a target of targeted therapy for HCC.