AbstractFibrosis, an aberrant reparative response to tissue injury, involves a disruption in the equilibrium between the synthesis and degradation of the extracellular matrix, leading to its excessive accumulation within normal tissues, and culminating in organ dysfunction. Manifesting in the terminal stages of nearly all chronic ailments, fibrosis carries a high mortality rate and poses a significant threat to human health. Heme oxygenase‐1 (HO‐1) emerges as an endogenous protective agent, mitigating tissue damage through its antioxidant, anti‐inflammatory, and antiapoptotic properties. Numerous studies have corroborated HO‐1's potential as a therapeutic target in anti‐fibrosis treatment. This review delves into the structural and functional attributes, and the upstream and downstream pathways of HO‐1. Additionally, the regulatory networks and mechanisms of HO‐1 in cells associated with fibrosis are elucidated. The role of HO‐1 in various fibrosis‐related diseases is also explored. Collectively, this comprehensive information serves as a foundation for future research and augments the viability of HO‐1 as a therapeutic target for fibrosis.