The purpose of this study was to study the effects of serum folate and plasma pyridoxal 5′-phosphate (PLP) on plasma homocysteine, oxidative stress and antioxidant capacities in 44 hepatocellular carcinoma (HCC) patients and 56 healthy controls. The responses of folate, vitamin B-6, homocysteine, oxidative stress and antioxidant enzyme activities in HCC patients before and after tumor resection were also determined. Patients with HCC before tumor resection had significantly lower folate, PLP, homocysteine, glutathione peroxidase and superoxide dismutase levels, but higher malondialdehyde, total antioxidant capacity and glutathione S-transferase activity when compared with healthy controls. Oxidative stress was significantly decreased to a level similar to that of healthy controls after tumor resection in the HCC group. There were no associations of folate and PLP with plasma homocysteine, indicators of oxidative stress and antioxidant capacities. Serum folate and plasma PLP were not significant factors affecting plasma homocysteine, oxidative stress and antioxidant capacities in patients with HCC.