To investigate the influence on channel catfish(Ictalurus punctatus)liver toxicity and liver proteome change by the use of selenium-enriched yeast,Se-concentration in channel catfish liver was determined and the pathological change was monitored after selenium-enriched yeast feeding for 56 days.Proteins extracted from the liver of seleniumenriched yeast feeding channel catfishes and nonfeeding controls were separated by two-dimensional gel electrophoresis(2-DE),differentially expressed proteins between the two groups were analyzed using ImageMaster software and identified by online reversedphase nanoflow liquid chromatography coupled with ion trap mass spectrometry(LC-MS/MS).The average Se-concentration of liver form the non-feeding controls and the seleniumenriched yeast feeding ones were 0.15 mg/kg and 0.81 mg/kg.Significant difference was detected between these two groups(P<0.05).H.E staining of pathology from channel catfish liver showed that the seleniumenriched yeast group has obvious cell loose and cell fatty degeneration.15 differetial protein were found by 2-DE separation and ImageMaster software analysis.Of them,8 overexpressed proteins in seleniumenriched yeast were selected for MS analysis and identified successfully,including 3 uregulated proteins and 5 uniquely expressed proteins in selenium-enriched yeast group compared with the controls.These differential proteins correspond to chaperonin TCP1 subunit 8 and glyceraldehyde-3-phosphate dehydrogenase,4SNc-Tudor domain protein,adenosine kinase a,transketolase and alanyl-tRNA synthetaselike et al.Obvious toxicity was detected in the channel catfish liver after feeding with selenium-enriched yeast.Organic selenium might strengthen immune through 4SNc-Tudor protein involved signal transmission pathway.Differential proteins identified in our work could be specific biomarkers related to toxicity of organic Se to channel catfish.