Background: The garden snail, Helix aspersa, is a big land snail widely found in the Mediterranean countries. It is one of the most consumed species and widely used in zootherapy. Objective: The present study was carried out to investigate for the first time the first time the antitumor activity of an aqueous extract from Helix aspersa. Materials and Methods: The effect of H. aspersa extract was studied on a triple negative breast cancer cell line Hs578T. Firstly, the morphological changes and the mode of cell death induced by the extract have been evaluated by microscopy and acridine orange/ethidium bromide staining. The effect of the extract at dilution 0.1% and 1% was then tested on some genes, regulators of cell death and proliferation like tumor necrosis factor α (TNFα), NF- κB, and the tumor suppressor genes P53 and PTEN. Results: Data demonstrate that the extract induces necrosis in tumor cells. It enhances significantly the expression of TNFα; mRNA levels were 20 and 10 times more important in treated cells compared to nontreated cells. NF-κB and PTEN were inhibited with the dilution 1% after 8 and 24 hours of treatment. P53 expression was further inhibited but only with the highest dose, after 4, 8, and 24 hours. Conclusion: Our results show that H. aspersa extract has an antitumor activity against Hs578T cells; it is a potent stimulator for TNFα and a good inhibitor for NF-κB.