The purpose of this research is to determine the effective amount and validate the high-performance and low-cost liquid chromatography (HPLC) method for the simultaneous analysis of theophylline (TH) and guaifenesin (GF), which have a wide spectrum overlap, in the form of theophylline G syrup. In the presented method, the C8 column with a length of 4.6 mm and a particle size of 5 microns and the parameters of selectivity, calibration curve, range, linearity, precision, accuracy, detection limit and measurement limit were used to validate the analysis method. Is. The inhibition time of theophylline and guaifenesin was 3.3 and 6.5 minutes, respectively. The minimum detectable concentration and the minimum measurable concentration obtained were 1.94 and 4.05 μg/ml, respectively. The proposed method is very selective, sensitive and accurate and is suitable for the simultaneous analysis of TH and GF in syrup form. The absence of buffer and the use of a small amount of organic solvents increase the life of the column and reduce the cost of theophylline and guaiafensine analysis in the industry.