Objective: To fabricate a nanoparticle with the combination effect of chemotherapy, photothermal therapy and photodynamic therapy. Furthermore, its antimultidrug-resistant tumor effects in vitro were evaluated. Methods: DOX-HIT-NPs were self-assembled through the intrinsic interaction between D-α-tocopherol succinate (TOS), human serum albumin (HSA), indocyanine green (ICG) and Doxorubicin (DOX). The morphology and particle size were characterized. MCF-7/ADR cells were employed to investigate the cellular uptake of DOX-HIT-NPs. Fluorescence microscopy was used to observe the level of reactive oxygen species (ROS) in MCF-7/ADR cells. The cytotoxicity of DOX-HIT-NPs was detected by CCK8 assay. Results: The prepared DOX-loaded HIT-NPs were approximately spherical with particle size of 278.8 nm. It produced a good photothermal effect. DOX-HIT-NPs could promote the cellular uptake of DOX in MCF-7/ADR cells. Under laser irradiation, DOX-HIT-NPs could induce ROS generation and result in a significant inhibition effect against MCF-7/ADR cells. Conclusion: DOX-HIT-NPs were obtained successfully, and DOX-HIT-NPs had the effect of reversing tumor multidrug resistance in vitro.