In this study, multi-responsive hydrogels were prepared using spiropyran-conjugated chitosan networks. The intra/inter polymerization of methacrylamide chitosan chains, which interpenetrated into pre-formed poly(hydroxyethyl methacrylate) (pHEMA) hydrogels, and subsequent modification with spiropyran (SP) derivatives resulted in the formation of multi-responsive hydrogels. The photochromic properties of these hydrogels were investigated in response to specific light illumination or acid/base treatment. In this hydrogel system, the colorless spiro form (SP) of spiropyran reversibly isomerized into the ring-open, fluorescent merocyanine (MC) state upon specific light irradiation. The MC form could be further protonated by acid vapors, endowing the hydrogel a yellow color. This process could be reversed by NH3 treatment to obtain a purple hydrogel. It is expected that the synthetic method for spiropyran-modified hydrogels using novel chitosan networks described herein would contribute greatly to the development of photochromic materials and chemical sensors.