Glutathione S-transferase (GST) is an important detoxification enzyme in organisms. GSTs play an important role in responding to environmental stresses. This study aimed to identify the GST gene superfamily in silver sillago (Sillago sihama) and analyze its expression pattern under hypoxia stress. A total of 17 GST genes were identified in silver sillago. Phylogenetic analysis showed that the GST gene family contained two subgroups (cytosolic and MAPEGs), and lacked three subgroups (i.e. Pi, Kappa, and MGST2). Phylogenetic and syntenic analysis revealed that GST genes were conserved in evolution. Eight SsGSTs were significantly differentially expressed under hypoxia stress in silver sillago by RNA-seq and qRT-PCR analysis. The expression levels of SsMGST3b, SsGSTO1, SsGSTT1b and SsGSTR2 genes were significantly up-regulated after 4 h of reoxygenation in the gill tissue. In the heart tissue, the expression of SsGSTR3 was significantly up-regulated after 1 h of hypoxia while the expression levels of SsGSTT1b and SsFLAP genes were significantly down-regulated after 4 h of hypoxia. In summary, this study provides for the first time a comprehensive analysis of the GST gene superfamily of silver sillago.