Abstract: Objective: To explore the relationship between oxidative stress and hyperhomocysteinemia (HHcy), and analyze the possible pathogenic mechanisms of HHcy. Method: Sixty-seven HHcy patients and 34 healthy subjects (healthy control group) were collected from October of 2014 to May of 2015. The level of serum superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and malondialdehyde (MDA) were detected, and the correlation between SOD, T-AOC, MDA and Hcy were further analyzed. Result: The levels of serum MDA and T-AOC were both higher than those of healthy control group (U=471.5, P<0.01;U=186, P<0.01). The level of serum SOD was lower than that of healthy control group (U=194, P<0.01). Compared severe group with mild group in HHcy patients, the level of serum MDA was only increased (U=245, P=0.006). The other indexes were not significantly different between the two group(P>0.05). In addition, we found that the correlation of Hcy with MDA,T-AOC was positive (P<0.05) and the correlation of Hcy with SOD was negative (P<0.01). Conclusion: In HHcy patients, the oxidation and antioxidant imbalance leads to that the ability to scavenge the free radicals is evidently reduced, leading to the free radical accumulation, which destroys the cells and tissue. By detecting of the oxidative stress indicators of SOD, T-AOC and MDA, we can provide the foundation for the pathogenic mechanism, prevention and antioxidant therapy in HHcy patients.