OBJECTIVE：To study on the effect of iodine （I2） on the acid content titration in the preparations， and establish a method of eliminating I2 for accurate determination of total acid content. METHODS：Taking an example of Onychomycosis paint，I2 was reduced by sodium sulfide （Na2S） before titration analysis and compared with the standard method of traditional titration. According to the two methods of consumption of different sodium hydrate （NaOH） volume， the effect of I2 on the determination of total acid content in preparation was explored. RESULTS：Reduction method of Na2S can eliminate the effect of I2， the color of indicator changed acutely. The determined total acid and theoretical values were the same； the linear range of the concentration of total acid in onychomycosis paint was 3.926-7.290 mol/ml（r＝0.999 9）； RSDs of precision， stability and reproducibility tests were no more than 0.04％； average recovery was 99.91％-100.10％（RSD＝0.036％，n＝6）. CONCLUSIONS：I2 has effect on the determination of total acid content， the disproportion reaction of I2 can generate hydriodic acid that can interfere acid-base titration’s results， and the generated hydriodic acid can oxidize indicator to make the end point is not sensitive or even invariant color. Using Na2S can eliminate the effect of iodine on the preparation of acid titration， which has improved precision and reproducibility with accurate and reliable determination results.