Elevated serum immunoglobulin G4 (IgG4) is one of the important features of patients with IgG4-related diseases (IgG4-RD). But diagnosing these diseases using IgG4 alone is tricky because the tests can sometimes give inaccurate results. Our research is focused on studying the ratio of IgG4 to two other substances, immunoglobulin G (IgG) and immunoglobulin G1 (IgG1), in the blood. We hope this approach will lead to more accurate diagnoses of IgG4-RD. We conducted a study on 68 patients diagnosed with IgG4-related diseases (IgG4-RD) and 160 individuals suffering from other autoimmune diseases (AID) at our hospital between June 2018 and June 2022. Eighty healthy people who underwent physical examination in our hospital at the same time were randomly selected as controls, and medical records were collected for all subjects. The serum IgG and IgG subclasses were detected, and the IgG4/IgG and IgG4/IgG1 ratios were calculated. We found that patients with IgG4-RD have significantly higher average levels of serum IgG4 and more elevated IgG4/IgG and IgG4/IgG1 ratios compared to individuals with other AID patients and those in good health (p < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the diagnostic effectiveness area under the curve (AUC) of the serum IgG4/IgG ratio for IgG4-RD was 0.906 (95% confidence interval [CI], 0.865-0.947) and 0.921 (95% CI, 0.876-0.965) when comparing with other AID patients and healthy individuals, respectively. The optimal cut-off value for the IgG4/IgG ratio was 0.147 (with 72.1% sensitivity and 94.4% specificity) compared with AID patients and 0.129 (with 77.9% sensitivity and 96.2% specificity) compared with healthy individuals. Similarly, the AUC of the serum IgG4/IgG1 ratio for diagnosing IgG4-RD was 0.919 (95% CI, 0.882-0.956) and 0.916 (95% CI, 0.870-0.962) when compared with patients with other AID and healthy individuals, respectively. When we divided our study participants into a high IgG4/IgG ratio group (>0.129) and a normal IgG4/IgG ratio group (≤0.129) using a cut-off point of 0.129, we found through logistic regression analysis that those with a high IgG4/IgG ratio were more likely to be associated with IgG4-RD (odds ratio [OR], 31.25; 95% CI, 15.31-63.79; p < 0.001). Likewise, a high IgG4/IgG1 ratio was also significantly linked to an increased risk of IgG4-RD (OR, 36.39; 95% CI, 17.57-75.38; p < 0.001). The serum's IgG4/IgG and IgG4/IgG1 ratios are independently linked to IgG4-RD and are valuable in its diagnosis.