Abstract: Objective To investigate the value of detection of T lymphocyte subsets in peripheral blood combined with immunoglobulin in the diagnosis of hand-foot-mouth disease. Methods A total of 200 patients with hand-foot-mouth disease were selected as hand-foot-mouth disease study. In addition, 200 people with physical examinations in the same period were included as healthy control group. The disease detection rate, T lymphocyte subsets in peripheral blood and immunoglobulin levels were compared. Results The detection rate of T lymphocyte subsets in peripheral blood combined with immunoglobulin was significantly higher than that of single test(P<0.05). The levels of CD3⁺, CD4⁺, CD8⁺, immunoglobulin A and immunoglobulin G in hand-foot-mouth disease group were significantly lower than those in healthy control group, and the corresponding indexes of severe hand-foot-mouth disease patients were significantly lower than those in mild patients(P<0.05). There was no significant difference in immunoglobulin M level between healthy control group and hand-foot-mouth disease group, and mild and severe hand-foot-mouth disease patients(P>0.05). Conclusion Combined use of T lymphocyte subsets in peripheral blood and immunoglobulin detection has a higher value in diagnosis of hand-foot-mouth disease, which can accurately determine the severity of the disease.