It is urgently needed for effective treatments of extensive skin loss, wherein lack of angiogenesis is a major obstacle. In this study, we present a thermosensitive thiolated chitosan (CSSH) hydrogel conjugated with Histatin1 (Hst1) as a wound dressing to study its efficacy in enhancing the cell adhesion, spreading, migration, and angiogenesis. The composite hydrogels with gelation time of 5–7 min, showed a prolonged release of Hst1. Cell culture indicated that the adhesion, spreading, migration and tubule formation of HUVECs were promoted, especially for the Hst1-H group. The in vivo healing evaluation showed that the rate of recovery in Hst1-H group was increased to 84% at day 7, and the CD31 positive cells, vascular endothelial growth factor (VEGF) positive cells and aligned collagen fibers were significantly more than the controlled groups. Therefore, CSSH/Hst1 hydrogel is a promising candidate for wound healing by accelerating cell adhesion, migration and angiogenesis.