The synergistic effect of chemo-photothermal therapy by near-infrared light-responsive nanoparticles is being widely researched. The combination of chemo-photothermal effects reduces the regrowth of tumor residuals by enhancing therapeutic coverage when compared with a single treatment modality. In the current study, doxorubicin hydrochloride-loaded polyvinylpyrrolidone-copper sulfide nanoparticles (DP-CuS NPs) were synthesized by a facile one-pot method. DP-CuS NPs showed good muco-adherence and also acted as an efficient chemo-photothermal agent. The polyvinylpyrrolidone (PVP) coating prevented the aggregation of CuS NPs and helped in stabilizing the size (hydrodynamic diameter ̴35nm) of the synthesized nanoparticle. PVP also served as a cargo, enabling the loading of a chemotherapeutic drug (doxorubicin) with an efficiency of ̴75 %. The localized release of doxorubicin was achieved by photothermal/pH trigger upon DP-CuS NPs, enhancing therapeutic efficiency. DP-CuS NPs, when treated with breast cancer cell line (MCF 7), exhibited efficient cancer cell cytotoxicity (cell viability: ̴11 %) and photothermal triggered mucolytic properties. These nanoparticles were also effective in preventing the growth of residual cancer cells through their mucolytic property and chemo-photothermal dual therapeutic effect. © 2021