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Agarophyton vermiculophyllum is a commercially important red alga for agar production in the Northwest Pacific Ocean and is an invasive seaweed in Europe. High temperature is an important environmental stressor that influences its growth, metabolism, and migration. Nevertheless, little is known about the molecular mechanisms underpinning the response of A. vermiculophyllum to heat stress. Using RNA-sequencing, we performed the first comprehensive transcriptome analysis of A. vermiculophyllum under heat stress to explore and identify potentially important heat stress-responsive genes. After de novo assembly of the transcriptome, 55,486 unigenes were found, of which 39,687 unigenes (71.52%) were functionally annotated. In total, 2,923 differentially expressed genes (DEGs) were detected between heat-stressed and control samples. Heat shock proteins represented the most abundant DEGs. Transcript factors were also significantly differently expressed under heat stress. Meanwhile, the photoprotective mechanism based on PsbS (Photosystem II subunit S) related nonphotochemical quenching and PGR5 (proton gradient regulation 5) dependent cyclic electron flow around photosystem I was found to be promoted under heat stress, which may help A. vermiculophyllum to cope with the high temperature. This study lays an important foundation for further elucidation of the molecular mechanism underlying heat tolerance in A. vermiculophyllum. [ABSTRACT FROM AUTHOR]