We analysed the cold-responsive gene repertoire for a psychrophilic methanogen, Methanolobus psychrophilus R15 through genomic and RNA-seq assayed transcriptomic comparisons for cultures at 18°C (optimal temperature) versus 4°C. The differences found by RNA-seq analysis were verified using quantitative real time-PCR assay. The results showed that as in the Antarctic methanogen, Methanococcoides burtonii, genes for methanogenesis, biosynthesis and protein synthesis were all downregulated by the cold in R15. However, the RNA polymerase complex was upregulated at cold, as well as a gene cluster for a putative exosome complex, suggesting that exosome-mediated RNA decay may be cold-accelerated. Unexpectedly, the chaperonin genes for both thermosome and GroES/EL were all upregulated at 4°C. Strain R15 possessed eight protein families for oxygen detoxification, including both anaerobe-specific superoxide reductase (SOR) and the aerobe-typical superoxide dismutase (SOD)-catalase oxidant-removing system, implying the higher oxidative tolerance. Compared with a mesophilic methanogen, R15 survived in higher paraquat, a redox-cycling drug. Moreover, 71 one-component systems and 50 two-component systems for signal transduction ranked strain R15, together with M. burtonii, as being highly adaptive among archaea. Most of them exhibited cold-enhanced expression, indicating their involvement in cold adaptation. This study has added new perspectives on the cold adaptation of methanogenic archaea.