The changes in and relationship between oxidative stress and the glutathione (GSH) antioxidant system in the plasma and tissues of patients with hepatocellular carcinoma (HCC) before and after tumor resection have not been clearly determined. We investigated the changes in oxidative stress, GSH status and its dependent antioxidant enzyme activities in HCC patients before and after tumor resection, and to determine the association of oxidative stress with GSH and its dependent antioxidant enzyme activities in plasma and tissues. This study employed a cross-sectional design. Forty-four men and 16 women with HCC were recruited. Fasting blood was drawn on the day before the tumor resection and one month after the tumor resection. HCC tissue and adjacent normal liver tissue were obtained at the time of surgical resection. Patients had significantly increased plasma malondialdehyde (MDA) and oxidized-low density lipoprotein levels but decreased GSH and oxidized GSH levels before tumor resection compared with the corresponding post-resection values. GSH and trolox equivalent antioxidant capacity (TEAC) levels and activities of GSH peroxidase were significantly increased while MDA level was significantly lower in HCC tissue when compared with the adjacent normal tissue. The pre-resection plasma MDA level was significantly correlated with pre-resection plasma GSH concentration, and MDA level in HCC and adjacent normal tissues. Pre-resection plasma GSH concentration was significantly correlated with GSH and TEAC level in HCC tissue. HCC patients had increased oxidative stress, decreased GSH, and lower dependent antioxidant capacities before tumor resection. However, hepatocellular tumor had increased GSH and TEAC levels as well as GSH peroxidase activities which might protect itself against increased oxidative stress.