Mandarin fish (Siniperca chuatsi) has become one of the most commercially important freshwater aquaculture species in China because of its fast growth and high nutritional value. Here, the proteome of the spleen of pathogenetic and resistant mandarin fish on the 8th day after ISKNV infection were analyzed using Illumina NovaSeq 6000 and isobaric tag for relative and absolute quantitation. The spleen tissue of the control group (C), resistant group (K), and pathogenetic group (B) were collected at 8 dpc.