Objective:This experiment sought to investigate the EP3 receptor splice variants expression patterns in liver cancer cell lines and their functions in controlling hepatoma cell growth . Methods:WST assay was used to detect the growth of liver cancer cell induced by EP3 receptor agonist Sulprostone;Two-dimensional electrophoresis and mass spectrometry were used to detect the protein level in CCLP1 cells by EP3 receptor agonist sulprostone;Real-Time PCR was used to detect the expression of EP3 receptor splicing variants in liver cancer cell. Results:CCLP1 cells were treated with 10 μmol/L sulprostone for 24 h,the results of cell growth rate increased to 131.46%(P < 0.01)detected by WST assay;CCLP1 cells were treated with 10 μmol/L Sulprostone for 24h,two-dimensional electrophoresis and mass spectrometry were used to detect the protein level. The results showed that promoting cell proliferation,invasion and cell metabolism related proteins were increased,on the contrary that reducing the cell metabolism rate,slowing down the cell growth,invasion and inhibiting cell metabolism related proteins were reduced;EP3-4,EP3-5,EP3-6 and EP3-7 splice variants were observed in HUH-7,Hep3B,HepG2,HuCCT1 and CCLP1 cells. Conclusion:EP3 receptor promoted the proliferation of liver cancer cell by up-regulating proteins that promoting cell growth and metabolism at same time down-regulating proteins that inhibiting cell growth and metabolism. EP3-4,EP3-5,EP3-6 and EP3-7 splice variants were observed in HUH-7,Hep3B,HepG2,HuCCT1 and CCLP1 cells.