Scuticociliatia disease is a major threat to large yellow croaker Larimichthys crocea at the fry stage. In the previous study, a ubiquitin regulatory X domain-containing protein (UBXN1) gene was found to be involved in Scuticociliatia disease resistance through genome-wide association analysis. To further confirm its gene function in resistance against Scuticociliatia, we identified UBXN1 gene sequence and investigated its expression characteristics, as well as signal pathway. The complete cDNA sequence of UBXN1 was 915 bp, encoding 304 amino acids. The putative UBXN1 protein was evolutionarily conserved and contained a UBA and a UBX domain. Moreover, UBXN1 had varying degrees of expressions in different tissues, among which the highest expression was observed in brain, moderate expression was in liver, heart and kidney, and the lowest expression was in muscle by qRT-PCR detection. It also showed that induced expression was found in spleen, brain, liver, and kidney during the early phase of infection, and the expression gradually recovered to the control level at the late phase. Further subcellular localization analysis showed that UBXN1 uniformly distributed in cytoplasm and nucleus. In addition, 16 differentially expressed genes were found in a comparative transcriptome analysis between the UBXN1 over expression group and control vector group, including up-regulated genes RPL41/RPL39/XIST/RNA45SN4 and down-regulated genes ATP8/ND4L. These findings provide new insights into finfish UBXN1 and its potential regulatory signaling pathway.