Abstract: Objective　To observe levels of the serum albumin and their association with prognosis in children with hand-foot-and-mouth disease (HFMD) . Methods A total of 122 HFMD children admitted from 2011 to 2013 were selected and divided into three groups: common group (n=57), severe group (n=52) and critical group (n=13). Serum albumin levels, blood glucose levels, peripheral blood white cell counts of the children in the three groups were compared within 24 hours of admission. Moreover, the incidence of hypoalbuminemia and mortality of the children were analyzed in each group. Results In critical group, serum albumin levels were significantly decreased while blood glucose levels and peripheral blood white cell counts were significantly increased than those in the severe group and common group, and the differences were all statistically significant (all P<0.05). There were no significant differences in serum albumin levels, blood glucose levels and peripheral blood white cell counts between severe group and common group (all P>0.05). There was no hypoalbuminemia and death in severe group and common group. The percentage of hypoalbuminemia and mortality of children in critical group were higher than those in the other two groups (all P<0.01). Conclusions The mortality was extremely high in children with critical HFMD. The decrease of serum albumin levels was a high risk factor for death in children with critical HFMD. Early and dynamic monitoring serum albumin levels may be helpful in evaluation of disease condition and prognosis of HFMD.