Objective: To study the correlation between the expression of epithelial cell adhesion molecule (Ep-CAM) and the pathological characteristics and prognosis of hepatoblastoma in children. Methods: Ep-CAM expression in 62 cases of hepatoblastoma from January 2015 to January 2017 was detected by immunohistochemistry. The relationships between the Ep-CAM expression and the pathological characteristics (such as gender, age, pathological stage, and pathological type) were analyzed. The survival curve was drawn to analyze the correlation between the expression level of Ep-CAM and prognosis. Results: The positive rates of Ep-CAM expression in 62 cases of hepatoblastoma were 75.81% and 0.00%, respectively (P<0.05). The positive expression of Ep-CAM in hepatoblastoma was related to PRETEXT stage, but not related to age, sex, preoperative alpha-fetoprotein level and pathological type of children. The positive expression rates of Ep-CAM in cancer tissues of children with PRETEXT stage III and IV were significantly higher than those in PRETEXT stage I and II (P<0.05). The 2-year overall survival rates of Ep-CAM positive and negative children were 34.04% (16/47) and 86.67% (13/15), respectively, with significant difference (P<0.05). Log-rank analysis showed that the overall survival rate of Ep-CAM positive and negative children was significantly different (P<0.05). Conclusion: Ep-CAM protein is highly expressed in hepatoblastoma tissues and correlates with PRETEXT staging. Ep-CAM protein is a key factor affecting the prognosis of hepatoblastoma. It may be a new target for diagnosis and prognosis evaluation of hepatoblastoma.