Ethanolic extract of spores of Lycopodium clavatum L., reportedly has profound effect against liver disorders, but lacks adequate experimental validation. To test this claim, healthy inbred Swiss albino mice, Mus musculus, were divided into different groups: Gr.I mice were fed normal diet (negative control); Gr.II - fed normal diet plus ethanol; Gr.III - fed two carcinogens of liver, [0.06% p-dimethyl aminoazobenzene (initiator) and 0.05% phenobarbital (promoter)] known to induce hepatotoxicity and genotoxicity; Gr.IV- mice fed ethanol plus both the carcinogens, and Gr.V- fed carcinogens plus spore extract of Lycopodium clavatum. They were sacrificed at day 90 and 120 for histological studies of liver, assay of cytotoxicity markers and assessment of genotoxicity using endpoints such as chromosome aberrations, micronuclei, mitotic index in bone marrow cells and sperm head anomaly. Additionally, western blot for p53 protein expression and matrix metalloproteinase (MMP) activity in liver was compared among different groups of treated and control mice to evaluate its therapeutic potentials. Compared to Gr.III and IV, less number of mice developed tumors in Gr.V along with significant reduction in hepatotoxicity and genotoxicity, thereby validating its potential use against liver ailments as a herbal remedy.Keywords: p-dimethyl aminoazobenzene, phenobarbital, plant extract, amelioration.