Methanotrophic bacteria play a crucial role in mitigating methane emissions by oxidizing methane in diverse environments. However, the molecular mechanisms underlying their adaptation to salinity stress remain poorly understood. In this study, comparative proteomic analysis was performed to investigate the salinity response strategies of methanotrophic bacteria. Proteins were extracted from cultures grown under different salinity conditions and analyzed using LC–MS/MS. Protein identification and label-free quantification were performed using Proteome Discoverer. The dataset provides insights into metabolic pathways and regulatory mechanisms involved in salinity adaptation and methane metabolism in methanotrophs.