DHEA-Box Helicase 37 (DHX37) is a putative RNA helicase. It is involved in various RNA secondary structure alteration processes, including translation, nuclear splicing, and ribosome assembly. It is reported to be associated with the neurodevelopmental disorder with brain anomalies, and a recent study suggests that DHX37 is a functional regulator of CD8 T cells. Dysregulation of the CD8 T cell function is closely related to defective antitumor immune responses. In the present study, we investigated the expression, mutation, and prognostic role of DHX37 in human cancers, mainly by mining publicly available datasets. Our results suggested that DHX37 was significantly upregulated in 17 kinds of tumors. Mutations including deletions, insertions, and substitutions of DHX37 were widely detected. Besides, the expression of DHX37 was negatively correlated with immune-related genes PD-L1, RGS16, and TOX, and it was positively associated with TIM3, LAG3, and NCOR2. Through biofunctional analysis, we observed that DHX37 was significantly enriched in cancer-related pathways such as cell cycle, DNA replication, mismatch repair, RNA degradation, and RNA polymerase. In conclusion, the study explored the significance of DHX37 in human cancers. DHX37 may serve as a potential target for cancer immunotherapy.