In this study, a rapid, simple, highly sensitive and anti-interference method for the joint detection of four IgG subtypes is established by using Raman microspheres with four characteristic Raman spectra. The results show that the concentrations of IgG1 in the range of 0–1500 ng ml−1, IgG2 in the range of 0–1100 ng ml−1, IgG3 in the range of 0–88.7 ng ml−1, IgG4 in the range of 0–77.2 ng ml−1, it shows a good correlation with the response value of The Raman signal. The lowest detection limits are 25.4 ng ml−1, 21.7 ng ml−1, 1.6 ng ml−1, 1.7 ng ml−1, respectively. Reproducibility is good, the coefficient of variation of low, medium and high concentration standard solution are within 10%. The recoveries of four IgG subtypes are in the range of 90%–110%, and the accuracy of the method is good. The coefficients of variation between and within the three batches of reagents are all less than 11%, showing good precision. There is no cross reaction with Procalcitonin (20 ng ml−1), Interleukin-6 (1 ng ml−1) and bovine serum albumin (10 mg ml−1), and the specificity is good. Common interfering substances such as bilirubin, triglyceride and trisodium citrate do not affect the determination results, and heparin sodium only affects the determination results of IgG1. This method has good anti-interference ability. The method has high sensitivity, simple operation and strong anti-interference ability, and has good correlation with the IgG detection methods commonly used in clinic. This simple and quantitative method can be used for the rapid detection of IgG subtypes in the future, which can improve the efficiency of clinical diagnosis.