Traditional tissue closure methods, such as sutures and staples, can be invasive and lead to postoperative difficulties. Conversely, clinical bioadhesives often exhibit weak adhesion to wet tissue due to an interfacial water barrier. Inspired by the liquid-to-solid hardening mechanism of mussel underwater adhesion, this work introduces an acid-induced adhesive (AIA) with inherent self-hardening capabilities. The AIA, solely composed of poly(thioctic acid) (polyTA), was developed through the acid-induced phase transition from an aq. solution of arginine thioctate. PolyTA was a hydrophobic poly(disulfide)s linear polymer with abundant carboxyl groups. This composition enables it to evict the interfacial water, form a large number of hydrogen bonds, and engage in hydrophobic interactions with tissues. The self-hardening of AIA stems from the rearrangement of the hydrophobic polymer main chain, significantly enhancing the cohesion of this bioadhesive. Its lap-shear adhesion strength to wet and underwater porcine skin reaches up to approximately 184 and 173 kPa within 10 min, respectively. Beyond its tissue adhesion performance, AIA excelled in leak sealing, on-demand detaching, biodegradation, good biocompatibility, M2-phenotype macrophage polarization regulation, and cell migration promotion. This polyTA-based bioadhesive presents an ideal strategy for biomedical applications.