Melanoma is a serious malignant skin tumor. Effectively eliminating melanoma and healing after-surgical wounds are always challenges in clinical studies. To address these problems, we propose manganese-doped calcium silicate nanowire-incorporated alginate hydrogels (named MCSA hydrogels) for in situ photothermal ablation of melanoma followed by the wound healing process. The proposed MCSA hydrogel had controllable gelation properties, reasonable strength, and excellent bioactivity due to the incorporated calcium silicate nanowires as the in situ cross-linking agents and bioactive components. The doping of manganese into calcium silicate nanowires gave them excellent photothermal effects for eradicating melanoma effectively under near infrared (NIR) irradiation. Moreover, the synergistic effect of manganese and silicon in the MCSA hydrogel effectively promotes migration and proliferation of vascular endothelial cells and promotes angiogenesis. Hence, such bifunctional bioactive hydrogels could achieve combined functions of photothermal therapy and wound healing, showing great promise for melanoma therapy and tissue regeneration.