Pacific abalone Haliotis discus hannai is one of the most economically important marine shellfish and is mainly distributed in the cooler seas of northern China. The molecular reactions that occur in this species under high temperature conditions have not been determined. To understand the molecular mechanisms of this species under heat stress, transcriptomic analysis of the hepatopancreas was performed at 33°C (22°C was used for the control) for 1 h on an Illumina HiSeq 2500 platform (pooling of six animals into single RNA-sequencing libraries). The results showed that 17,852 unigenes were annotated. In all, 8,532 genes were significantly differentially expressed in the test group compared with the control group, including 4,788 upregulated and 3,744 downregulated genes. Enrichment analysis identified some noteworthy GO terms (cellular process and response to stimulus) and pathways (protein processing in the endoplasmic reticulum (ER) and apoptotic signaling pathways), and these were further analyzed. Analysis showed that genes indicative of mitochondrial damage were upregulated; DNA damage formation, and fatty acid and amino acid synthesis increased; fatty acid decomposition reduced; and misfolded proteins accumulated in the ER, and the unfolded protein response and ER-associated degradation were triggered to relieve ER stress. In addition, the apoptotic pathway was activated; however, some genes associated with anti-apoptosis and molecular chaperones were upregulated to maintain homeostasis after heat stress. These data provide an increased understanding of the heat stress mechanisms in Pacific abalone.