With the continued advancement in the design and engineering of hydrogels for biomedical applications, there is a growing interest in imparting stimuli-responsiveness to the hydrogels in order to control their physicomechanical properties in a more programmable manner. In this study, an in situ forming hydrogel is developed by cross-linking alginate with an elastin-like polypeptide (ELP). Lysine-rich ELP synthesized by recombinant DNA technology is reacted with alginate presenting an aldehyde via Schiff base formation, resulting in facile hydrogel formation under physiological conditions. The physicomechanical properties of alginate-ELP hydrogels can be controlled in a wide range by the concentrations of alginate and ELP. Owing to the thermoresponsive properties of the ELP, the alginate-ELP hydrogels undergo swelling/deswelling near the physiological temperature. Taking advantage of these highly attractive properties of alginate-ELP, drug release kinetics were measured to evaluate their potential as a thermoresponsive drug delivery system. Furthermore, an ex vivo model was used to demonstrate the minimally invasive tissue injectability.