Channa striatus is a large-bodied fish of freshwater habitat capable of withstanding hypoxic conditions. Adaptive response to hypoxia is a complex physiological process. A laboratory -based rearing protocol for investigating long-term hypoxia stress tolerance in this species was established. Using suppression subtractive hybridization technique, we examined gene expression patterns in liver during prolonged hypoxia exposure. A total of 130 transcripts from the enriched cDNA library, under hypoxic condition, were sequenced. BLAST analysis identified 58%, 18% and 24% as known, uncharacterized and unknown sequences, respectively. All known genes represented a broad spectrum of biological pathways such as transcription/translation, signal transduction, electron transport, immune response, reproduction, cellular transportation. Heightened abundances for 11 Known, 1 uncharacterized and 1 unknown mRNA in the hypoxic liver were documented. Among these, the full-length cDNA sequences for heat shock protein 90 and CSHL-338 clone (uncharacterized) were generated using RACE strategy. Full-length cDNA sequences of prefoldin and fatty acid binding protein was obtained from the respective clones of SSH cDNA library, were also up -regulated during hypoxia stress. In this study, possible physiological significances about hypoxia-tolerance transcripts have been discussed. The ESTs presented here will have potential future implications in exploring new mechanisms of hypoxia acclimation and/or tolerance in C. striatus.