The filamentous fungus strain Fusarium sp. ZW-21 was used for ethanol production with corncob hydrolysate. The fermentation conditions of ethanol production from corncob hydrolysate by the strain were investigated, and the effect of temperature, pH, nitrogen source, and surfactants on the ethanol production was investigated. The two factors yeast extract and polysorbate 80 were selected for further optimization by response surface methodology. The optimal conditions for ethanol production by the strain Fusarium sp. ZW-21 were 50 g/L sugar of corncob hydrolysate, 10.35 g/L yeast extract, 10 g/L KH2PO4, 0.5 g/L MgSO4·7H2O, 0.38 g/L polysorbate 80, pH 6.0, inoculum size of 1 mL/50 mL medium, and incubation temperature of 30 °C. The fermentation period was 5 d under oxygen-limited conditions, and the ethanol yield was 24.2 g/L.