Abstract: Methods for the determination of residues of 3 monomers, including methacrylic acid (MAA), 3-(methacryloyloxy) propyltris (trimethylsiloxy) silane (TRIS) and 1,1,3,3,3-hexafluoroisopropylisobutenolate (HFIPM) in orthokeratology lens by gas chromatography (GC) and high performance liquid chromatography (HPLC) were proposed, and the results of methodology validation and sample determination using the two methods were compared. The lens sample no less than 200 mg was placed into a vacuum drying oven and dried at (60±5)℃ under vacuum condition for no less than 24 h to constant weight. The sample with constant weight was put into a Soxhlet extractor, and 100 mL of dichloromethane was added for heating 4-6 h. The extraction solution was transferred into a 100 mL-volumetric bottle and diluted with dichloromethane to obtain the test solution. In the GC method, the separation was performed on DB-WAX capillary column (30 m×0.32 mm, 0.5 μm) by column temperature program with nitrogen as carrier gas, and the targets were detected by flame ionization detector. In the HPLC method, the separation was carried out on CAPCELL PAK C₁₈ MGⅡcolumn (150 mm×4.6 mm, 5 μm) by gradient elution with the mixed solution composed of 0.1% (volume fraction) phosphoric acid solution and acetonitrile at different volume ratios as mobile phase, and the targets were detected by diode array detector. The results showed that the same linear range of the standard curves obtained by GC was 1.0-1 000 mg·L^-1, with detection limits in the range of 0.006%-0.010%, and the linear ranges of the standard curves obtained by HPLC were 0.1-200 mg·L^-1 for MAA and HFIPM, and 1.0-1 000 mg·L^-1 for TRIS, with detection limits in the range of 0.001%-0.009%, indicating that GC was suitable for the determination of high residual samples and HPLC was suitable for the determination of low residual samples. The recoveries measured by GC were in the range of 89.1%-111%, with RSDs (n=6) of the determined values ranged from 0.83% to 4.1%, and the recoveries measured by HPLC were in the range of 90.5%-108%, with RSDs (n=6) of the determined values ranged from 0.92% to 4.7%. There was no significant difference between the two methods by F-test and t-test analysis at the significance level of 0.05. Three batches of orthokeratology lenses from different manufacturers were tested for residue and migration. The results showed that residual amount of TRIS was detected in three batches of samples, and the maximum migration amount of TRIS was 0.112%. Residual amount of MAA was detected in two batch of samples, and residual amount of HFIPM was detected in one batch of sample, but MAA and HFIPM were not detected in the migration test.