Harmful algal blooms (HABs) caused by harmful cyanobacteria adversely impact the water quality in aquatic ecosystems and burden socioecological systems that are based on water utilization. Currently, Korea uses the Environmental Fluid Dynamics Code-National Institute of Environmental Research (EFDC-NIER) model to predict algae conditions and respond to algal blooms through the HAB alert system. This study aimed to establish an additional deep learning model to effectively respond to algal blooms. The prediction model is based on a deep neural network (DNN), which is a type of artificial neural network widely used for HAB prediction. By applying the synthetic minority over-sampling technique (SMOTE) to resolve the imbalance in the data, the DNN model showed improved performance during validation for predicting the number of cyanobacteria cells. The R-squared increased from 0.7 to 0.78, MAE decreased from 0.7 to 0.6, and RMSE decreased from 0.9 to 0.7, indicating an enhancement in the model’s performance. Furthermore, regarding the HAB alert levels, the R-squared increased from 0.18 to 0.79, MAE decreased from 0.2 to 0.1, and RMSE decreased from 0.3 to 0.2, indicating improved performance as well. According to the results, the constructed data-based model reasonably predicted algae conditions in the summer when algal bloom-induced damage occurs and accurately predicted the HAB alert levels for immediate decision-making. The main objective of this study was to develop a new technology for predicting and managing HABs in river environments, aiming for a sustainable future for the aquatic ecosystem.