In a recent experiment, we discovered that liver tissue adjacent to HCC can also produce des-gamma-carboxy prothrombin (DCP). The goal of this study was to advance measurements of DCP levels in hepatocellular carcinoma (HCC) and non-cancer tissues using an electro-chemiluminescence immunoassay (ECLIA) and immunohistochemistry, and to assess their clinical significance. DCP levels in HCC tissues ranged from 0.7 to 209862.4 mAU/0.1 g tissue weight, with a median of 492.6 mAU/0.1 g. DCP levels in non-cancer tissues ranged from 0 to 2329.9 mAU/0.1 g tissue weight, with a median of 88.8 mAU/0.1 g. DCP levels in cell membranes were significantly higher than in the cytoplasm (p<0.001). DCP levels in HCC tissue were significantly higher than in non-cancer tissue (p<0.001). The logarithm of serum DCP levels correlated not only with that of DCP levels in HCC tissues (p=0.019), but also with that in non-cancer tissues (p=0.020), and the total DCP level of liver tissues (p=0.016). The logarithm of DCP levels in HCC tissues correlated with that of DCP levels in non-cancer tissues (p=0.011). DCP levels in HCC tissue with portal vein invasion were significantly greater than in HCC tissues without portal vein invasion (p=0.028). DCP levels in non-cancer tissues with intrahepatic metastatic lesions were significantly higher than in non-cancer tissues without intrahepatic metastatic lesions (p=0.023). Our results suggest that the origin of elevated serum DCP may lie not only in HCC tissue, but in non-cancer tissue. The existence of HCC may influence production of DCP in non-cancer tissue. Tissue DCP may be a prognostic factor, while increased DCP levels in non-cancer tissues may play an important role in hepatocarcinogenesis.