Abstract: Objective To investigate the expression of STC2 (stanniocalcin-2, STC2) in patients with hepatocellular carcinoma and analyze the clinical significance in pathological features as well as prognosis. Methods The real-time RT-PCR and immunohistochemical method was used to detect the expression of STC2 in hepatocellular carcinoma, and the relationship among STC2, clinicopathological features and prognosis of hepatocellular carcinoma of the esophagus were analyzed. Results The positive rate of STC2 expression in hepatocellular carcinoma was 82.00%(82/100), which was higher than that in the non- hepatocellular carcinoma tissues[37.00%(37/100)], there was significant difference(χ²=42.017, P<0.01). The expression of STC2 was associated with tumor size (χ²=5.978, P=0.041), differentiation grade (χ²=19.06, P=0.001), tumor TNM stage (χ²=12.348, P=0.001) and portal vein tumor thrombus (χ²=11.718, P=0.001); the expression of STC2 had no correlation with gender (χ²=0.130, P=0.719), age (χ²=2.944, P=0.080), tumor number (χ²=1.967, P=0.132), and liver cirrhosis (χ²=0.014, P=0.638). The Kaplan-Meier survival curve showed that hepatocellular carcinoma patients with positive STC2 had shorter overall survival than that of patients with negative STC2(t=5.632, P=0.017). The result of real-time PCR showed that mRNA expression of STC2 was also significantly reduced in hepatocellular carcinoma tissues (t=8.273, P<0.01). Conclusion The aberrant expression of STC2 may be related to the occurrence and development of hepatocellular carcinoma and it may be a potential molecular target for treatment.