Aim: methotrexate was formulated as Ethosomal gel for enhancing the therapeutic performance and stability to treat cervical cancer via targeting the drug locally through cervical mucosa to avoid the systemic adverse effect of the chemotherapy. Materials and Methods: The formulations were produced using phospholipid and cholesterol then evaluated for particle size, polydispersity index, zeta potential, pH and drug release. The optimized ethosome formula then converted to gel. The gel evaluated for organoleptic properties, pH, viscosity and permeability. Results: The results showed than F8 was the best ethosomal formula with 34nm in size and 92% entrapment efficiency. This formula converted into gel had 1% gelling agent that was optimized ethosomal gel formula and gave better release that ordinary methotrexate gel with same type and percent of gelling agent. Conclusions: The drug was successfully formulated as ethosomal gel for treating cervical cancer topically in order to avoid the systemic exposure for the chemotherapy and its consequence adverse effect.