Abstract: Objective:To explore the levels of serum immunoglobulin IgG subclass, complement C3 and C4, and C reactive protein(CRP) in children with hand-foot-mouth disease(HFMD) and its clinical significance. Methods:One hundred and three severe HFMD children and 301 common HFMD children were divided into the severe and common groups, 50 healthy children were set as the control group. The serum levels of immunoglobulin IgG subclass, complement C3 and C4, and CRP in 3 groups were detected. Results:The levels of immunoglobulin IgG1 and IgG3, complement C3 and C4 in severe group were significantly lower than those in control group and common group(P<0.01), the level of CRP in severe group were significantly higher than that in the control group and common group(P<0.01). The differences of the levels of immunoglobulin IgG1, IgG2, IgG3 and IgG4, complement C3 and C4, and CRP between the common group and control group were not statistically significant(P>0.05). Conclusions:The humoral immune response in severe HFMD children is abnormal, children can be secondarily bacteria infected on the basis of virus infection. The combined detections of immunoglobulin IgG subclass, complement C3 and C4, and CRP has certain clinical significance in understanding the progress of the HFMD.