The significance of flu prediction is that the appropriate preventive and control measures can be taken by relevant departments after assessing predicted data; thus, morbidity and mortality can be reduced. In this paper, three flu prediction models, based on twitter and US Centers for Disease Control's (CDC's) Influenza-Like Illness (ILI) data, are proposed (models 1-3) to verify the factors that affect the spread of the flu. In this work, an Improved Particle Swarm Optimization algorithm to optimize the parameters of Support Vector Regression (IPSO-SVR) was proposed. The IPSO-SVR was trained by the independent and dependent variables of the three models (models 1-3) as input and output. The trained IPSO-SVR method was used to predict the regional unweighted percentage ILI (%ILI) events in the US. The prediction results of each model are analyzed and compared. The results show that the IPSO-SVR method (model 3) demonstrates excellent performance in real-time prediction of ILIs, and further highlights the benefits of using real-time twitter data, thus providing an effective means for the prevention and control of flu.