The invention discloses an oil-in-water compound ketoconazole nano-medicament. The grain diameter of the medicament is 1-100nm. The oil-in-water compound ketoconazole nano medicament comprises the following raw materials in percentage by weight: 0.01-8.0 percent of ketoconazole, 0.01-10 percent of eugenol, 0.001-5.0 percent of clobetasol propionate, 25.0-45.0 percent of surfactant, 0-10.0 percentof cosurfactant, 0.1-25.0 percent of oil and the balance of distilled water. The oil-in-water compound ketoconazole nano-medicament can be used for treating stubborn skin mycotic infection, mycodermatitis, chronic mucocutaneous candidiasis, dermatitis blastomycosis, coccidioidomycosis, histoplasmosis, chromoblastomycosis and paracoccidioidomycosis, and dermatomycosis and tinea versicolor caused by dermatophyte and microzyme as well as trichophyton disease, scytitis and pruritus. The oil-in-water compound ketoconazole nano-medicament has the advantages of strong osmosis, favorable stability, favorable infiltrating property, durable acting time, remarkable effect, low cost, simple preparation method and convenience in popularization and application.