In the present study, alginate/cartilage extracellular matrix (ECM)-based injectable hydrogel was developed incorporated with silk fibroin nanofibers (SFN) for cartilage tissue engineering. The in situ forming hydrogels were composed of different ionic crosslinked alginate concentrations with 1% w/v enzymatically crosslinked phenolized cartilage ECM, resulting in an interpenetrating polymer network (IPN). The response surface methodology (RSM) approach was applied to optimize IPN hydrogel's mechanical properties by varying alginate and SFN concentrations. The results demonstrated that upon increasing the alginate concentration, the compression modulus improved. The SFN concentration was optimized to reach a desired mechanical stiffness. Accordingly, the concentrations of alginate and SFN to have an optimum compression modulus in the hydrogel were found to be 1.685 and 1.724% w/v, respectively. The gelation time was found to be about 10 s for all the samples. Scanning electron microscope (SEM) images showed homogeneous dispersion of the SFN in the hydrogel, mimicking the natural cartilage environment. Furthermore, water uptake capacity, degradation rate, cell cytotoxicity, and glycosaminoglycan and collagen II secretions were determined for the optimum hydrogel to support its potential as an injectable scaffold for articular cartilage defects.