Abstract: As a non-invasive treatment, phototherapy shows important application prospect in cancer treatment. However, the clinical application of phototherapy is greatly restricted by its low penetration depth, strong oxygen dependence, and high incidence of immune and inflammatory reactions. Gas therapy based on endogenous gases (e.g. nitric oxide, carbon monoxide, hydrogen sulfide) possesses the advantages of low toxicity and endogeneity. The combination of phototherapy and gas therapy can not only achieve greater therapeutic effect, but also avoid unnecessary damage caused by phototherapy. This review introduces the application of phototherapy, gas therapy and synergistic therapy in tumor diagnosis and treatment, elaborates the challenges and opportunities of phototherapy combined with gas therapy, and discusses mainly the way to rationally construct a nanosystem for synergistic therapy to further promote its clinical application.