In recent years, hyperthermia as a treatment method for malignant tumors, has been widely used in clinical settings. Hyperthermia can effectively prevent the recurrence and metastasis of malignant tumors, and improve the quality of life and prolong the survival period of the patients, but the anticancer mechanism of hyperthermia is not clear. For gaining insight into the mechanism of action of hyperthermia against malignant tumors, the authors, in this paper, summarize the recent researches about hyperthermia and eukaryotic translation initiation factor 5A (eIF5A), which demonstrate that eIF5A has a relative high expression in colorectal cancer, gastric cancer and other malignant tumors, and plays an important role in promoting the proliferation, invasion and metastasis of tumor cells, and eIF5A expression level declines in different degrees in gastric cancer and colon cancer cells after hyperthermia, indicating that eIF5A may play an important role in the action of hyperthermia on malignant tumors.