The invention relates to a method of using a liquid chromatography tandem mass spectrometry for synchronously measuring four kinds of antibiotics in river sediment. The method of using the liquid chromatography tandem mass spectrometry for synchronously measuring the four kinds of antibiotics in the river sediment includes the following steps that 1, an experimental vessel is prepared; 2, the moisture content is measured; 3, vacuum freeze drying is conducted; 4, sequential extraction, grinding and sieving are conducted; 5, ultrasonic extraction and mechanical vibration are used for preparation; 6, double-column tandem solid-phase extraction is carried out, wherein before the solid-phase extraction, a buffer solution is added into an extraction solution subjected to rotary evaporation, then, ultrapure water is adopted to dilute a mixture, and the mixture is shaken to be fully uniform; 7, the extraction solution is purified and subjected to elution; 8, concentration and constant volume are conducted; 9, high-performance liquid chromatography is adopted to carry out synchronous computer measurement. By the adoption of the method of using the the liquid chromatography tandem mass spectrometry for synchronously measuring the four kinds of antibiotics in the river sediment, the purification and enrichment effects are greatly improved, 0.2% methanoic acid-2mmol / L ammonium acetate is used, acetonitrile and a citric acid buffer solution of which the pH value is 3 are used as the extraction solution of a solid sample, and optimal conditions are adopted to be configured and combined,so that a target analyte is better isolated, chromatographic peak area is larger, and the recovery rate is higher.