The matricullular protein CCN1 (CYR61) is essential for cardiovascular development during embryogenesis, whereas in adulthood it is associated with inflammation, wound healing, injury repair, and related pathologies including fibrosis and cancer. Recent studies have found that CCN1 plays a critical role in promoting wound healing and injury repair in a variety of organs and tissues, including the skin, liver, and intestine. Mechanistically, CCN1 functions through direct interaction with specific integrin receptors expressed in various cell types in the wound tissue microenvironment to coordinate diverse cellular functions for repair. We will discuss the current knowledge on the functions of CCN1 in tissue injury repair and pertinent unanswered questions.