Tissues and organs get exposed to high oxygen (O-2) supply in hyperoxia conditions. The goal of this research was to investigate the protective effect of actin binding protein gelsolin on hyperoxia-induced hepatotoxicity through histopathology and measurement of oxidative stress parameters and DNA damage in a neonatal Wistar albino rats. The pups were randomly separated to four equal groups such as: normoxia control group (NC), normoxia plus gelsolin group (NG, 10 ng/kg bw/day gelsolin), hyperoxia (>= 85% O-2) group (HC), hyperoxia plus gelsolin group (HG, >= 85% O-2; 10 ng/kg bw/day gelsolin). Histopathological changes of pups in hyperoxia condition were revealed in the form of severe leukocyte infiltration, vascular congestion, necrosis, vacuolar degeneration, binucleated hepatocytes and hemorrhage in the liver tissue. SOD, CAT, GPx and GST activities decreased and MDA level increased in the hyperoxia-induced group in liver tissue (P < 0.05). Tail DNA%, tail length and moment indicating DNA damage statistically increased in hyperoxia treatment groups when compared to controls. Treatment of rats with hyperoxia plus gelsolin prevented hyperoxia-induced changes in tissue structure, antioxidant enzyme activities and MDA level, mean tail DNA% and length. Based on these findings, gelsolin restored these changing to near normal levels but it does not protect completely in the hyperoxia conditions.