Naphthenic acid in diesel was removed by complex deacidification agents consisting of sodium hydroxide and ethanol. The effect of all parameters on removing naphthenic acid from diesel was reviewed systematically. On the basis of single factor experiments, orthogonal experiments were performed to optimize the deacidification process. The results showed that the optimum deacidification process was that the volume ratio of sodium hydroxide to ethanol was 2:1, the volume ratio of complex deacidification agents to diesel was 1.4:1, the reaction temperature was 303 K, the reaction time was 50 s, and the standing time was 30 min. The acidity of the diesel was reduced from 135.52 mg KOH/100 mL to 4.52 mg KOH/100 mL, and the deacidification rate reached 96.66% under the optimum process; thus the treated diesel met the quality requirements.