Objective: To investigate the clinical value of preoperative serum levels of carbohydrate antigens (CA19-9, CA50, CA242, CA125) and carcino-embryonic antigen (CEA) in predicting resectability of pancreatic head cancer. Methods: The clinical data of 104 patients with cancer in the head of the pancreas admitted between January 2014 and December 2015 were analyzed retrospectively. The serum tumor markers associated with the resectability of pancreatic head cancer were picked up, and their predictive values for the resectability of pancreatic head cancer were determined by receiver operating characteristic curve (ROC) and the area under ROC curve (AUC). Results: All the 104 patients received surgical exploration, by which, the tumors in 54 cases were considered resectable (resectable group), and in 50 cases were unresectable (unresectable group). The preoperative serum CA50 and CEA levels showed significant difference between the two groups (both P>0.05), while the preoperative serum CA19-9, CA242 and CA125 levels in unresectable group were significantly higher than those in resectable group (317.99 kU/L vs. 152.98 kU/L; 67.81 kU/L vs. 39.36 kU/L; 71.53 kU/L vs. 29.22 kU/L, all P<0.05). ROC analysis showed that both CA19-9 and CA125 had predictive significance for the resectability of pancreatic head cancer, with the optimal cut-off value of 236.13 kU/L and 16.44 kU/L, and AUC of 0.667 and 0.678 respectively, while lone detection of CA242 had no predictive significance for the resectability of pancreatic head cancer (AUC=0.609, P=0.085). The sensitivity and specificity for predicting resectability of pancreatic head cancer were increased by combined detection of CA19-9 and CA125. Conclusion: Preoperative serum CA19-9 and CA125 levels can be used as auxiliary indicators for estimating the resectability of pancreatic head cancer, and their combined detection may increase the diagnostic sensitivity and specificity.