Abstract: OBJECTIVE To develop a solid-phase extraction (SPE)-high performance liquid chromatographic( HPLC ) method for the simultaneous determination of tartrazine, sunset yellow, ponceau 4RC and amaranth in Child Paracetamol, Artificial Cow-bezoar and Chlorphena Mine Maleate granules. METHODS The granule sample was dissolved in water, and the solution was purified and enriched by a polyamide SPE column. The eluate obtained was analyzed by HPLC method with Inertsil ODS-3 C₁₈ column(4.6 mm×250 mm, 5 μm), methanol-0.02 mmol·L^-1 ammonium acetate solution as mobile phase with gradient elution. For quantitative analysis, the detection was performed at the maximum absorption of the synthetic colors, they were 428 nm(tartrazine), 521 nm (sunset yellow), 509 nm (ponceau 4RC) and 483 nm (amaranth). The column temperature was 30 ℃ and the flow rate was 1.0 mL·min^-1. RESULTS The linear ranges of tartrazine, sunset yellow, ponceau 4RC and amaranth were 0.05-4 μg·mL^-1(r≥0.999 5). The average recoveries were 98.0%(RSD=0.52%), 97.9%(RSD=0.38%), 98.6% (RSD=0.27%) and 99.5% (RSD=0.43%), respectively. CONCLUSION The method is simple, accurate, and reproducible, can be used for the quality control of 4 synthetic colors in Child Paracetamol, Artificial Cow-bezoar and Chlorphena Mine Maleate granules.