Ring finger protein 122 (RNF122), an E3 ubiquitin ligase, orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination. However, its functional relevance in teleosts has yet to be clearly defined, particularly regarding the identification of substrate-specific regulatory sites. This study characterized RNF122 from mandarin fish ( ), termed RNF122, and investigated its regulatory impact on stimulator of interferon genes (STING)-mediated antiviral signaling. Results showed that RNF122 expression was up-regulated in response to mandarin fish ranavirus (MRV) infection, and its overexpression suppressed STING-mediated interferon (IFN) production and enhanced MRV replication. Co-immunoprecipitation confirmed a direct interaction between RNF122 and STING. Functional assays demonstrated that RNF122 facilitated STING degradation through the ubiquitin-proteasome pathway, a process impeded by MG132 treatment. Ubiquitination analyses of various STING mutants revealed that RNF122 catalyzed STING ubiquitination at K95, K117, and K155 residues. Moreover, RNF122 significantly impaired STING-dependent antiviral responses by engaging negative regulatory elements within the signaling cascade. Overall, RNF122 was identified as a negative modulator of STING-mediated IFN signaling in mandarin fish, diminishing STING-dependent antiviral activity and promoting its degradation via the ubiquitin-proteasome pathway at lysine residues K95, K117, and K155. These findings provide mechanistic insight into the post-translational control of STING in teleosts and establish a foundation for future investigations into antiviral immune regulation.