Objective: To investigate the guiding significance of the criteria of TNM classification (6th edition) developed by American Joint Committee on Cancer (AJCC) in estimating prognosis of primary liver cancer (PLC). Methods: A total of 2 456 PLC patients undergoing liver resection recorded in the seer database between 2004 and 2010 were included in this study. Of the patients, 2 270 cases (92.4%) had hepatocellular carcinoma (HCC), 145 cases (5.9%) had intrahepatic cholangiocarcinoma (ICC), and 41 cases (1.7%) had combined HCC and ICC (cHCC-ICC). The overall survivals (OS) of the patients with different types of PLC were analyzed and compared, and the relations of TNM classification with the prognosis of the patients were also analyzed. Results: The 1-, 3-, and 5-year OS was 83.0%, 58.1% and 46.6% in HCC patients, 80.0%, 45.5% and 26.2% in ICC patients and 63.4%, 29.3% and 29.3% in cHCC-ICC patients respectively, and the OS in the former was significantly better than those in the latter two groups (P=0.049, 0.004), but showed no statistical difference between the latter two groups (P>0.05). For HCC or ICC, the OS in patients with TNM stage I was significantly better than those in patients with other TNM stages (all P<0.05), but no statistical difference was noted among patients in different stage III stratifications (IIIA, IIIB, IIIC) (both P>0.05); for cHCC-CC patients, the OS had no statistical difference among patients of all TNM stages (P>0.05). The presence of lymph node metastasis (N1) in PLC was rare (3.9%), and OS showed no statistical difference among HCC, ICC and cHCC-CC patients with N0 disease (P>0.05). Conclusion: There are some limitations in TNM staging system for estimation of prognosis of PLC, so some new pathological indicators should be incorporated into the system so as to satisfy clinical needs.