Previous research has extensively studied the seasonalities of human influenza infections and the effect of specific climatic factors in different regions. However, there is limited understanding of the influences of monsoons. This study applied generalized additive model with monthly surveillance data from mainland China to explore the influences of the East Asian Monsoon on the spatio-temporal pattern of seasonal influenza in China. The results suggested two influenza active periods in northern China and three active periods in southern China. The study found that the northerly advancement of East Asian Summer Monsoon (EASM) influences the summer influenza spatio-temporal patterns in both southern and northern China. At the interannual scale, the north-south converse effect of EASM on influenza activity is mainly due to the converse effect of EASM on humidity and precipitation. Within the annual scale, influenza activity in southern China gradually reaches its maximum during the summer exacerbated by the northerly advancement of EASM. Furthermore, the winter epidemic in China is related to the low temperature and humidity influenced by the East Asian Winter Monsoon (EAWM). Moreover, the active period in transition season is related partially to the large rapid temperature change influenced by the transition of EAWM and EASM. Despite the delayed onset and instability, the climatic condition influenced by the East Asian Monsoon is one of the potential key drivers of influenza activity.