Sofosbuvir (S) (sovaldi) is a nucleotide analog, which is a highly active NS5B polymerase inhibitor in HCV. Sovaldi has shown high efficacy against HCV in combination with and without PEG-INF, among other medications. Ribavirin (R) is an antiviral drug which is non-selective, antihepatitis. Ribavirin has only been used in combination for treating chronic HCV infection. Silymarin (SL) is a natural antioxidant derived from the seeds and fruits of the Silybum marianum plant(Milk thistle). It's known for its impact on hepatoprotection. The goal of this study is to determine the protective effect of silymarin on the chromosome and sperm as a natural product against the side effects of sofosbuvir and ribavirin as an antiviral drug. Intraperitoneally (i.p.), male albino mice (weight 25–30 g) were injected with Sofosbuvir at a dose level of 50 mg / kg / day, ribavirin at a dose level of 20, mg / kg / day, and Silymarin at a dose level of 70 mg / kg / day injections for five consecutive days, by various means. Mice were slaughtered 24 hours later. Chromosomal abnormalities and morphology of the sperm head were studied using classical cytogenetic methods. Tests showed that Sofosbuvir and Ribavirin caused abnormalities in the structural chromosomal aberration and sperm head. Although silymarin induces reduction in all injected forms of these abnormalities.