A rapid method for the simultaneous determination of 21 illegally added compounds in health foods was developed based on solid phase extraction (SPE) combined with ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). After ultrasonic extraction with acetonitrile, the samples were purified on an HLB SPE column, separated on a Waters BEH C18 column (100 mm×2.1 mm, 1.7 μm) using 10 mmol/L ammonium acetate aqueous solution and methanol as the mobile phases. The compounds were detected by an electrospray ionization (ESI) source in positive ion mode with multi-reaction monitoring (MRM). The 21 illegal additives showed good linear relationships with correlation coefficients no less than 0.995. The limits of detection (LODs) were 3-160 μg/kg for different matrixes. The recoveries ranged from 61.8% to 109.3%, and the relative standard deviations ranged from 1.6% to 14.7%. The method can be used for the simultaneous determination of the illegally added drugs in the losing weight, lipid-lowering, anti-diabetic and anti-hypertension health foods.