Mammalian hibernation is a strategy employed by many species to survive fluctuations in resource availability and environmental conditions. Hibernating mammals endure conditions of dramatically depressed heart rate, body temperature, and oxygen consumption; yet show no typical pathological response. Because of the high abundance and metabolic cost of skeletal muscle, not only must it adjust to the constraints of hibernation, but is positioned to play a more active role in the initiation and maintenance of the hibernation phenotype. In this study, MS/MS proteomic data were searched against a custom database of transcriptomic and genomic protein predictions built using the platform GalaxyP. This proteogenomic approach allows for a thorough investigation of skeletal muscle protein expression throughout the circannual cycle of the 13-lined ground squirrel. Of the 1,563 proteins identified by these methods, 232 were differentially expressed. Not only do these data support previously reported physiological transitions, they also offer insight into specific mechanisms of how their muscles might be reducing nitrogenous waste, preserving mass and function, and signaling to other tissues. Additionally, the combination of proteomic and transcriptomic data provides unique opportunities for determining the level of post-transcriptional regulation throughout the year and improving the genomic annotation of this non-model organism.