BACKGROUND: As an alternative form of cancer therapy, photothermal therapy (PTT) and sonodynamic therapy (SDT) using nanomaterials are in development. Nanomaterials can act as energy absorber as well as anti-cancer agent. OBJECTIVE: In this study, the effects of laser and ultrasound irradiation with Se-PEG-Cur nanoparticles were investigated on melanoma cancer. MATERIAL AND METHODS: In this experimental study, nanoparticles of selenium-polyethylene glycol-curcumin (Se-PEG-Cur) were synthesized, and their UV-vis absorption, particle size, zeta potential and photothermal conversion efficiency were determined. Se-PEG-Cur was then introduced as a novel 808-nm laser light absorbing agent as well as ultrasound (US) wave for treatment of C540 (B16/F10) cancer cells. Also, ROS generation in C540 (B16/F10) cancer cells was measured upon PTT and SDT using Se-PEG-Cur. RESULTS: Mean size, zeta potential and photothermal conversion efficiency of Se-PEG-Cur were obtained as ~300 nm, 42.7 mV and 16.7%, respectively. Cell viability upon irradiation of the laser light or US waves with 100 µg mL Se-PEG-Cur were decreased to 33.9 and 22.9%, respectively. CONCLUSION: Intracellular ROS detection indicated that dual PTT and SDT in the presence of Se-PEG-Cur induced the highest ROS production. Se-PEG-Cur was therefore introduced as an absorbing agent of both laser light and US waves for cancer treatment.