〔Abstract〕 Objective To investigate the cytotoxic effects of doxorubicin(Dox)-loaded nanoparticles based on hollow copper sulfide(CuS) on the human pancreatic cancer cell line BxPC-3,to achieve the combination of chemotherapeutic drugs and photothermal therapy, and to enhance the killing effect of chemotherapy on pancreatic cancer. Methods Hollow CuS nanoparticles, PEG-modified nanoparticles and DOX@PEG-CuS nanoparticles were synthesized and characterized. BxPC-3 cells were divided into four groups,BxPC-3 cells+PBS,BxPC-3 cells+Free DOX, BxPC-3 cells+PEG-CuS, BxPC-3 cells+DOX@PEG-CuS. Inductively coupled plasma mass spectrometry was used to detect the cellular uptake of BxPC-3 cells. MTT assay and dead and alive staining assay were used to detect the killing effect of each experimental group on pancreatic cancer cell line BxPC-3. Results CuS nanoparticles with a size about 356.3 nm were successfully prepared, and after surface modification with PEG, the particle size of the PEG-CuS nanoparticles was about 209.8 nm. CuS nanoparticles modified by PEG are stable in 10% serum. The results of ICP-MS showed that PEG-CuS uptake rate of pancreatic cancer cells increased with the incubation time at 2 h(12.95%), 4 h(20.20%) and 6 h(32.98%)(P<0.05,t=4.083;P<0.01,t=5.889). The results of MTT method showed after combined photothermal therapy and chemotherapy, the doxorubicin-loaded CuS had the best killing effect, and the killing rate of pancreatic cancer cells was up to 88.3%, which was better than 52.04% of the CuS treatment group alone(F=711.6,P<0.000 1) and 45.58% of the free Dox group(F=711.6,P<0.000 1). Conclusion The hollow copper sulfide particles modified by PEG can be stably present in 10% serum. The uptake rate of CuS nanoparticles increases with time after PEG modification. Photothermal therapy combined with chemotherapy can achieve a higher killing effect on pancreatic cancer cell line BxPC-3.