Tumor microenvironment (TME) dynamics and the critical dual role of hydrogen sulfide (H2S) in prostate cancer (PCa) biology are discussed in the present review. PCa remains one of the most prevalent malignancies in men, with advanced castration‑resistant PCa presenting substantial therapeutic challenges. H2S, an endogenous gaseous signaling molecule, is a key regulator of biological processes, including immune modulation, cell proliferation and apoptosis, during tumor progression. H2S exhibits paradoxical effects in PCa by promoting tumorigenesis and exerting context‑dependent antitumor activity. H2S mediates these outcomes through key signaling pathways, including the PI3K/AKT and MAPK/ERK pathways, which regulate tumor cell survival and metastasis. The present review emphasizes how H2S regulates tumor cell dynamics and immune interactions in a concentration‑dependent manner within the TME, making it a promising therapeutic target to overcome resistance to conventional treatments. Future research should prioritize translating these findings into clinical strategies, particularly through the development of H2S‑modulating therapies tailored to the TME, offering potential for overcoming resistance in advanced PCa.

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