Objective To explore the risk factors in disease progression and the significance of vascular endothelial growth factor ( VEGF ) and vascular intercellular adhesion molecule-1 ( VCAM-1 ) in hand foot and mouth disease ( HFMD) combined with encephalitis .Methods Altogether 92 subjects with HFMD were enrolled in the study and were divided into four groups , including group A ( ordinary group with no complication ) , group B ( severe group with complication ) , group C ( critical group with complication ) , group D ( recovery group with complication ) .Concentrations of VEGF and VCAM-1 in serum and cerebro-spinal fluid were detected by double antibody sandwich ELISA method .Multiple factors logistic regression analysis was performed to analyze main risk factors in disease progression for two combinations , one for ordi-nary group and severe group , the other for severe group and critical group .The results were analyzed by SPSS16.0 statistical software.Results The concentration of VEGF and VCAM-1 in serum and cerebrospi-nal fluid had statistically significant differences among the four groups , but there was no significant difference between group A and group D , and between group B and group C .In addition , the statistically significant factors for prediction of disease progression were duration of fever , limb shaking, cerebrospinal fluid WBC , cerebrospinal fluid protein and EV 71 IgM between ordinary group and severe group , and cerebrospinal fluid WBC, respiratory rate and heart rate between severe group and critical group .The multiple factors logistic regression analysis revealed that limb shaking , cerebrospinal fluid protein , VEGF and VCAM-1 in serum were the main risk factors for disease progression from ordinary to severe (P=0.071, 0.019, 0.020, 0.025 and OR=147.629, 26.572, 5.958, 6.345).And increased heart rate indicated the progression from se-vere to critical with P value of 0.001 and OR value of 2.69.Conclusion (1) Compared with group A, VEGF and VCAM-1 in serum and cerebrospinal fluid were highly expressed in patients with HFMD combined with encephalitis .Therefore , VEGF and VCAM-1 could be used as diagnostic criteria for auxiliary diagnosis of encephalitis in patients with HFMD and reflect the severity and prognosis to a certain extent .( 2 ) Risk factors like limb shaking , cerebrospinal fluid protein , VEGF and VCAM-1 in serum would be helpful to early diagnosis of severe patients .Increased heart rate would be a significant factor for identification of patients with critical disease , according to which a timely treatment would be provided to prevent from worse .