Objective To develop a gas chromatography-mass spectrometry solid-phase extractionfor detectingphthalic acid esters (PAEs) in the serum of patients with thyroid cancer. Four PAEs, namely, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), and di (2-ethyl) hexyl phthalate (DEHP), were used in experiments. Methods Samples of PAEs were extracted and enhanced using a solid-phase extraction glass column. The column temperature parameters were as follows: the initial temperature was${60}^{\circ}\mathrm{C}$. The temperature was maintained at${60}^{\circ}\mathrm{C}$for 1 min and then increased by${20}^{\circ}\mathrm{C}/\mathrm{{min}}$to${220}^{\circ}\mathrm{C}$. The temperature was then increased by${5}^{\circ}\mathrm{C}/\mathrm{{min}}$to${290}^{\circ}\mathrm{C}$and maintained at${290}^{\circ}\mathrm{C}$for 2 min. The mass spectrometry conditions were as follows: the ionization mode was electron impact, the source energy was${70}\mathrm{{eV}}$, the ion source temperature was${240}^{\circ}\mathrm{C}$, the quadrupole temperature was${150}^{\circ}\mathrm{C}$, and the scanning mode was selective ion monitoring (SIM). These parameters were qualitatively based on the target compound’s retention time and the mass-to-charge ratio (m/z). Quantitative analysis was conductedusing the standard internal method. Results The standard curve regression equations of DMP, DEP, DBP, and DEHP all had excellent linear relationships with correlation coefficients greater than 0.997. The precision of DMP, DEP, DBP, and DEHP was 2.60%, 4.73%, 5.50% and 5.70%, respectively. The average recoveries were in the average range of${94.5}\%$. The detection rate of DBP, DMP, DEP and DEHP were 100%,31.6%,73.46%, and${100}\%$, respectively. Conclusion The method is suitable for simultaneous detection of PAEs in human serum, with low organic dose, short extraction time, good recovery and reproducibility, and low detection limit.