Objective The present study evaluated the left ventricular systolic function using twodimensional speckle tracking imaging (2DSTI) in patients with Handfootmouth disease (HFMD).Methods m41 children hospitalized with HFMD caused by EV71 were recruited in the experimental group, which were further separated into mild and severe groups based on the severity. 21 healthy subjects were used as control. LVEF (Simpson) and Tei index was acquired. Then，using 2DSTI for calculation of global longitudinal strain (GLS). The clinical characteristics and echocardiographic findings were compared. Results An increase of WBC count, heart rate, blood glucose, CRP, CK, and CK-MB levels was detected in severe HFMD group (P＜0.05) compared to mild HFMD and control groups. There was no different of clinical features between mild HFMD and control groups. Severe HFMD patients experienced lower LVEF and GLS, and higher Tei index compared to mild HFMD and control groups (P＜0.01). Mild HFMD group, on the other hand, had comparable LVEF, Tei index, and GLS as the control group. The severe HFMD group had lower LPSS on LV inferior, lateral, epical, and mid and basalinferoseptal segments compared to control group. Compared to the mild HFMD group, the severe HFMD group was detected lower LPSS on basaland midinferior, midand epicallateral, midand epical inferoseptal, and epical segments. And the mild HFMD group exhibited lower LPSS on lateral and basaland midinferior segments compared to the control group.Conclusion HFMD patients experienced segmental and global cardiac systolic dysfunction. 2D STI has high sensitivity to detect the changes of cardiac function, provide information for early diagnosis and cure.