This review systematically delineates the dual roles of HYAL1 in cancer: on one hand, by degrading HA to generate low-molecular-weight fragments with pro-angiogenic and immunomodulatory activities, HYAL1 promotes tumor progression and metastasis in various malignancies, including prostate cancer, esophageal carcinoma, and osteosarcoma; on the other hand, it demonstrates tumor-suppressive properties in specific contexts such as colorectal cancer models. Here, HYAL1 is linked to Familial prostate cancer.