Background: Repeated heating degrades cooking oil quality, increasing peroxide values above national safety standards (SNI 01-3741-2002). Household waste cooking oil typically reaches 20-40 meq/kg, potentially triggering systemic oxidative stress and organ toxicity.Objectives: To analyze the mechanism of waste household oil as a trigger of oxidative damage leading to DNA oxidation.Methods: This prospective, controlled, true experimental in vivo time-course study initially allocated 32 male Swiss Webster mice into four parallel cohorts (n=8 per group), with 28 completing the final analysis (n=7 per group). The mice were orally treated with used cooking oil at a dosage of 10 μl/g body weight. The animals were distributed into four experimental cohorts. Group A (control) received fresh oil (peroxide value 8-10 meq/kg) for eight weeks, while Groups B, C, and D received waste oil (peroxide value 20-40 meq/kg) for 8, 12, and 16 weeks, respectively. Following the treatment, assays evaluated serum MDA and SOD, hepatic 8-OHdG via HPLC, TNF-α and IL-6 expression via IHC, and liver histopathology (congestion, steatosis, and necrosis) via H&E staining. Data were analyzed using the Kruskal-Wallis and Wilcoxon-Mann-Whitney post-hoc tests.Results: Used cooking oil administered over a 16-week period led to an increase of harmful effects. These included oxidative stress, primarily through lipid membrane peroxidation, evidenced by significant increases in both serum MDA and activated SOD p<0.05. The oil also induced chronic inflammation, marked by elevated expression of TNF-α and IL-6 in the cytoplasm and sinusoids. Furthermore, it resulted in severe liver structure changes (including congestion, steatosis, and necrosis) and a time-dependent upward trend in 8-OHdG, reaching statistical significance at 16 weeks compared to controls (p<0.05).Conclusion: These findings suggest that prolonged consumption of household used cooking oil promotes progressive hepatic lipid peroxidation and structural damage, with oxidative DNA damage accumulating significantly after extended exposure (16 weeks).