Harsh thermal environments in the rocky intertidal zone pose serious physiological and molecular challenges to the inhabitants. Metabolic depression is regarded as an energy-conserving feature of intertidal species. To understand the molecular mechanism of metabolic depression, we investigated physiological and transcriptomic responses in the intertidal snail Echinolittorina radiata. The metabolic rate and expression of most genes were insensitive to temperatures ranging from 33 to 45 °C and then increased with further heating to 52 °C. Different from other genes, the genes involved in heat shock response (HSR) and oxidative stress response (OSR) (e.g., genes encoding heat shock protein 70 (HSP70) and cytochrome P450 protein (CYP450)) kept upregulating during metabolic depression. These high levels of HSR and OSR genes should be important for surviving the harsh thermal environments on the rocky shore. In the population experiencing more frequent moderate heat events, the depression breadth was larger, and the change in magnitude of upregulation was insensitive for HSR genes (e.g., HSP70s) but heat-sensitive for OSR genes (e.g., CYP450s) at the temperature of 37 to 45 °C. These findings indicate that both the thermal sensitivity of HSR and OSR genes and the insensitivity of metabolic genes are crucial for surviving extreme intertidal environments, and different populations of the same species rely on various physiological mechanisms to differing extents to deal with heat stress. The cellular stress response is not a “one size fits all” response across populations largely depending on local thermal regimes.