Objective: To investigate the expression of epidermal growth factor receptor ErbB4 in human intrahepatic cholangiocarcinoma (ICC) tissues and its significance. Methods: The ErbB4 expressions in 24 paired specimens of ICC tissue (ICC group) and adjacent bile duct tissue (tumor adjacent group), and 16 specimens of bile duct tissue from hepatolithiasis patients (hepatolithiasis group) were detected by immunohistochemical staining, and the relations of ErbB4 expression with the clinicopathologic factors of ICC patients were also analyzed. Results: The strong positive expression rate of ErbB4 in ICC group was 75.0%, which was significantly higher than that in tumor adjacent group (45.8%) or hepatolithiasis group (37.5%) (both P<0.05), nuclear expression rate of ErbB4 in ICC group was significantly higher than that in the other two groups (both P<0.05), while the membranous and cytoplasmic expression rates of ErbB4 showed no significant difference among the three groups (both P>0.05). High ErbB4 expression was significantly associated with lymph node metastasis and TNM stage of ICC patients (both P<0.05). Conclusion: Increased expression of ErbB4 and its transfer into cellular nucleus are closely related to the occurrence and development as well as infiltration and metastasis of ICC.