Hand, foot, and mouth disease (HFMD) is a contagious viral illness that commonly affects infants and children. This infection is an emerging infectious disease in Rizhao in recent years. The present study examined the short-term effects of meteorological factors on adolescent HFMD in Rizhao. A generalized additive Poisson model was applied to estimate the effects of meteorological factors on adolescent HFMD occurrence in 2010-2012. Subgroup analyses were also conducted to examine the potential effect modifiers of the association in terms of age, sex, and occupation. A positive effect of temperature was observed (ER excess risk=1.93%, 95% CI: 1.05 to 2.82% for 1°C increase on lag 5 day). A negative effect of relative humidity at lag 1 day and positive effects were found on lag 5-7 days, and an adverse effect was observed for sunshine at lag days 3-4 (ER=−0.71%, 95% CI: −1.25 to −0.17% on lag day 4). We also found that age, sex, and occupation might be important effect modifiers of the effects of weather variables on HFMD. This study suggests that meteorological factors might be an important predictor of adolescent HFMD occurrence in Rizhao. Age, sex, and occupation might be important effect modifiers of the effects.