In order to solve the problems of the traditional Hand-Foot-Mouth Disease (HFMD) incidence trend prediction algorithm, such as low prediction accuracy, lack of the combination of other influencing factors and short prediction time, a method of long-term prediction using meteorological factors and Long Short-Term Memory (LSTM) network was proposed. First, the sliding window was used to convert the incidence sequence into the input and output of the network. Then, the LSTM network was used for data modeling and prediction, and the iterative prediction was used to obtain the long-term prediction results. Finally, the temperature and humidity variables were added to the network to compare the impact of these variables on the prediction results. Experimental results show that adding meteorological factors can improve the prediction accuracy of the model. The proposed model has the Mean Absolute Error (MAE) on the Jinan dataset of 74.9, and the MAE on the Guangzhou dataset of 427.7. Compared with the commonly used Seasonal Autoregressive Integrated Moving Average (SARIMA) model and Support Vector Regression (SVR) model, the proposed model has the prediction accuracy higher, which proves that the model is an effective experimental method for the prediction of the incidence trend of HFMD.