Background: Genotoxicity due to the effect of anti-cancer drugs on the healthy cells in cancerous patients is one of the problems of chemotherapy. Mitoxantrone is a chemotherapy anti-cancer drug, which can have side effects on the healthy cells like secondary cancers. On the other side, Melatonin is a hormone that is responsible for the daily rhythm adjustment and has several properties to be anti-cancer and anti-inflammation, and therefore it has a genoprotective effect against the genotoxicity. Recently, it has been shown that all living cells produce ultraweak photon emission (UPE) spontaneously and continuously. The intensity of UPE is in the order of a few, up to 104 photon/(cm2 sec) (or 10âˆ’19 to 10âˆ’14 W/cm2) measurable by photodetectors. UPEs are produced from diverse natural oxidative and biochemical reactions, especially free radical reactions and the simple cessation of excited molecules. Also, it has been evidenced that UPE has a signaling role at a distance among different cell cultures.Objective: Here, we investigate the effect of UPE among similar cells (i.e. â€œAutooptic effectâ€) by using mirrors around the cell plate(s). Here, we have used HepG2 as sample cancer cells.Methods: In this study, the HepG2 cells were co-treated by melatonin as a genoprotective and silver nanoparticles as a carrier against mitoxantroneâ€™s genotoxicity. Our results are analyzed based on the Comet assay method, and the genoprotective effect of melatonin is investigated in presence of (and without) mirrors against the genotoxicity of mitoxantrone. Additionally, the autooptic effect is investigated in presence of Ag nanoparticles (NPs).Results: The obtained results indicate that Ag NPs with lower concentrations of melatonin made more protection as genoprotective agent, and the same results obtained by increasing accessâ€™ cells to drug.Conclusion: The autooptic effect could increase the genoprotective effect of melatonin.