Progresses in the medicinal application of nanocompounds were accepted for the treatment of cancer. Nanoparticles-based therapy is of benefit for effective biodistribution and specific targeting. The current study investigated the anticancer effect of green synthesized platinum nanoparticles (PtNPs) against colon cancer cells (HCT-116). Flow cytometry and ELISA techniques were employed for detecting apoptotic and oxidative stress markers. Furthermore, PtNPs-lycopene (PtNPs-LP) on cell migration and invasion of HCT-116 cells was also examined. The PtNPs-LP was capable of diminishing cell proliferation and viability of HCT-116 cells in a dose-dependent mode. After treatment with PtNPs-LP, a significant increase in pro-apoptotic Bax and caspase-3 and a decrease in anti-apoptotic Bcl-2 was observed in treated cells that subsequently released cytochrome C into its cytoplasm, initiating cell death. Moreover, PtNPs-LP induced excessive generation of reactive oxygen species (ROS) and oxidative stress in cancer cells. In conclusion, PtNPs-LP exerts an antitumor effect against colon cancer cells via mediating important mechanisms such as cytotoxicity, apoptosis, and oxidative stress.