There has been a growing interest in the use of Shilajit powder as an adjuvant for the treatment of various ailments. This study sought to evaluate the preventive and restorative potentials of Shilajit in a model of spleen toxicity induced by mercury chloride in rats and its effects on the MLH1 gene expression. Four groups of twenty male Wistar rats (n =5) were created at random. Group, I was the untreated control group. Group II was given an intraperitoneal (IP) dose of HgCl2 at 1mg/kg body weight for 3 weeks. Group III was given an oral dose of Shilajit extract (500 mg/ kg b.w) daily for 3 weeks and then HgCl2 at a dose of 1 mg/kg b.w /IP daily for 3 weeks. Group IV received an oral dose of 500 mg/kg body weight of Shilajit extract for 3 weeks after receiving an IP dose of HgCl2 at 1 mg/kg body weight for 3 weeks. Bodyweight, relative spleen weight, hematological parameters, tissue oxidative stress, the expression of the MLH1 gene, and spleen histology were evaluated. The results showed that HgCl2 administration to rats altered the hematological parameters and spleen histology in addition to leading to a decrease in the spleen’s GSH content and an increase in lipid peroxidation. However, the oral administration of Shilajit in the preventive model showed more potency in preventing the toxicity caused by HgCl2 exposure. Therefore, more research is required to clarify the restorative potentials of Shilajit on HgCl2-induced spleen toxicity.