Objective: Lycopene (C40H56), a carotenoid found in red colour fruits, is known as a powerful antioxidant that protects cells from damage caused by reactive oxygen species (ROS). Etoposide inhibits topoisomerase II activity and restricts the development of cancer cells, though it establishes oxidative stress. To study the effect of lycopene (Ly) against hepatotoxicity and testis injury induced by etoposide in male rats. Settings: The experiment lasted for seven consecutive weeks including one week as acclimatization time. Design: The experiment was in a completely randomized design with a 2x2 factorial arrangement. Intervention(s): The animals were grouped as follow: No etoposide injection and no lycopene (control), lycopene supplementation (LY), etoposide injection (ET), and rats with etoposide injection and lycopene supplement (ET+LY). Main Outcome Measure(s): At the end of the experiment, rats were sacrificed by cervical dislocation. Blood samples were harvested and analyzed for serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TP), glucose (GLU) and testosterone. The left testis was manipulated for histological examination. Result(s): The result of experiment showed that rats with etoposide injection had higher ALT, AST, and ALP than the control rats. In contrast co-treated rats (ET+LY) significantly modulated the levels of the hepatic parameters. Administration of lycopene increased testosterone concentration and germinal epithelium of seminiferous tubules in testes rats. Conclusion(s): Lycopene might be a promising agent with hepatoprotective effect in restoring testis injury induced by etoposide in rats. (Fertil Steril Sci (R) 2023;4:30-5. (c) 2022 by American Society for Reproductive Medicine.)