Some genetic alterations of glutathione S-transferase omega 2 (GSTO2) have been reported to increase the risk of many malignancies, including hepatocellular carcinoma (HCC); however, their prognostic capability remained unresolved in HCC patients treated with transarterial chemoembolization (TACE). To fill this gap, we genotyped three well-defined polymorphisms in GSTO2 to assess whether they can predict overall survival among 228 HCC patients under TACE treatment. The median follow-up time and survival time were 22.0 months (range 3.0-60.0) and 19.2 months, respectively. Only one of three polymorphisms examined, rs157077, was significantly associated with overall survival of TACE-treated HCC (P = 0.003), and its mutant allele conferred a higher risk of death than its wild homozygotes (hazard ratio 1.58, 95 % confidence interval 1.17-2.14). Moreover, carriers of this mutant allele had higher tissue GSTO2 expression, reinforcing the prognostic capability of GSTO2 rs157077 for HCC, especially in combination with age and tumor-node-metastasis (TNM) stage. Taken together, we for the first time provided evidence supporting the prognostic role of GSTO2 in the progression of TACE-treated HCC.