In the context of climate change, understanding how indigenous amphibians of the Qinghai-Tibet plateau react to stresses and their coping mechanisms could be crucial for predicting their fate and successful conservation. A liver transcriptome for Nanorana pleskei was constructed using high-throughput RNA sequencing, and its gene expression was compared with frogs acclimated under either room temperature or high temperature and also heat wave exposed ones. A total of 126,465 unigenes were produced, with 66,924 (52.92%) of them being annotated. Up to 694 genes were found to be differently regulated as a result of abnormal temperature acclimatization. Notably, genes belonging to the heat shock protein (HSP) family were down-regulated in both treated groups. Long-term exposure to high-temperature stress may impair the metabolic rate of the frog and trigger the body to maintain a hypometabolic state in an effort to survive challenging times. During heat waves, unlike the high-temperature group, mitochondrial function was not impaired, and the energy supply was largely normal to support the highly energy-consuming metabolic processes. Genes were more transcriptionally suppressed when treated with high temperatures than heat waves, and the body stayed in low-energy states for combating these long-term adverse environments to survive. It might be strategic to preserve initiation to executive protein activity under heat wave stress. Under both stress conditions, compromising the protection of HSP and sluggish steroid activity occurred in frogs. Frogs were more affected by high temperatures than by heat waves.