Objective: To develop an HPLC method for determination of naphazoline hydrochloride, diphenhydram hydrochloride and lidocaine hydrochloride added in nasal cold compress gel (dew), and to establish an HPLC-triple quadrupole mass spectrometry (HPLC-MS) method to confirm the positive samples. Methods: The samples were extracted with acetonitrile, detected by high performance liquidchromatography, quantified by external standard method and confirmed by HPLC-MS. The separation was performed on a XTerra RP18 (150 mm×4.6 mm, 5 μm) column with the mobile phase consisting of 50 mmol·L^-1 ammonium acetate (the pH value was adjusted to 7.8 with acetic acid or ammonia solution)-acetonitrile (72∶28) at the flow rate of 1.0 mL·min^-1 and the detection wavelength was 230 nm. The analysis was performed on a BEH C₁₈ (100 mm×2.1 mm, 1.7 μm) column with a gradient elution of 0.1% formic acid aqueous solution-0.1% formic acid acetonitrile solution. The column temperature was set at 40 ℃ and the flow rate was 0.4 mL·min^-1. Electrospray ionization source was applied and operated in positive electrospray ionization and the multiple reaction monitoring mode. Results: The method showed the lowest detection concentrations of naphthazoline hydrochloride, diphenhydramine hydrochloride and lidocaine hydrochloride were 2.4 ng·mL^-1, 50 ng·mL^-1 and 50 ng·mL^-1. The sample recoveries ranged from 93.9% to 104.6%. Good linearities were found in the concentration range of 10-200 μg·mL^-1（r>0.999 0）. A total of 42 batches of samples were detected and the total positive rate was 70% (36/42). Naphthazoline hydrochloride were found in 34 batches. Diphenhydramine hydrochloride and lidocaine hydrochloride were found in 2 batches simultaneously. Conclusion: The established method is specific, sensitive, simple, accurate and reliable. It can be used for the qualitative and quantitative determination of naphthazoline hydrochloride, diphenhydramine hydrochloride and lidocaine hydrochloride in nasal cold compress gel (dew).