Heat shock transcription factors (HSFs) are an essential plant-specific transcription factor family that regulates the developmental and growth stages of plants, their signal transduction, and their response to different abiotic and biotic stresses. The HSF gene family has been characterized and systematically observed in various species; however, research on its association with Lycoris radiata is limited. This study identified 22 HSF genes (LrHSFs) in the transcriptome-sequencing data of L. radiata and categorized them into three classes including HSFA, HSFB, and HSFC, comprising 10, 8, and 4 genes, respectively. This research comprises basic bioinformatics analyses, such as protein sequence length, molecular weight, and the identification of its conserved motifs. According to the subcellular localization assessment, most LrHSFs were present in the nucleus. Furthermore, the LrHSF gene expression in various tissues, flower developmental stages, two hormones stress, and under four different abiotic stresses were characterized. The data indicated that LrHSF genes, especially LrHSF5, were essentially involved in L. radiata development and its response to different abiotic and hormone stresses. The gene–gene interaction network analysis revealed the presence of synergistic effects between various LrHSF genes’ responses against abiotic stresses. In conclusion, these results provided crucial data for further functional analyses of LrHSF genes, which could help successful molecular breeding in L. radiata.