Abstract: Objective To identify the significance and effect on prognosis of ERK-1 and Cyclin D1 expression levels in hepatocellular carcinoma (HCC). Methods Fifty specimens of HCC, 17 specimens of adjacent non-cancerous cirrhosis hepatic tissue and 14 specimens of normal hepatic tissue were fixed by 10% formaldehyde,embeded in paraffin after excision. ERK-1 and Cyclin D1 were detected with immunohistochemistry. Results 1. ERK-1 and Cyclin D1 expression frequency in HCC were significantly higher than that in adjacent non-cancerous hepatic tissue and in normal hepatic tissue. 2. ERK-1 expression obviously correlated with clinical stage, the pathological classification, age, the size of tumor and the portal vein tumor thrombosis. 3. Cyclin D1 expression only related with the pathological classification. 4. Both ERK-1 and Cyclin D1 negative or weak expression, the survival rate was lower and the prognosis was poorer. Both ERK-1 and Cyclin D1 moderate and strong expression, the survival rate was higher and the prognosis was better. 5. ERK-1 expression level was positively correlated with Cyclin D1 expression level in HCC. Conclusion Increased the expression of ERK-1 and Cyclin D1 played an important cooperative and stimulative role in hepatocellular carcinoma. Monitoring the expression of ERK-1 and Cyclin D1 greatly help early diagnosed the hepatocellular carcinoma and evaluated the patients' prognosis.