High mobility group box 1 (HMGB1) is widely expressed in mammalian tissues and cells which is involved in various pathophysiological processes such as inflammation, autophagy, and apoptosis, and plays an important role in maintaining cell survival and normal function. HMGB1 plays an important part in the development of stroke, which can affect the prognosis by inducing neuroinflammation and autophagy. HMGB1 may have a bidirectional effect in acute and chronic phases. Exploring the specific role and mechanism of HMGB1 in each stage of stroke may make it a new target for prevention and treatment in the future.