Abstract Spatio-temporal prediction is a key type of tasks in urban computing, e.g., traffic flow and air quality. Adequate data is usually a prerequisite, especially when deep learning is adopted. However, the development levels of different cities are unbalanced, and still many cities suffer from data scarcity. To address the problem, we propose a novel cross-city transfer learning method for deep spatio-temporal prediction tasks, called RegionTrans. RegionTrans aims to effectively transfer knowledge from a data-rich source city to a data-scarce target city. More specifically, we first learn an inter-city region matching function to match each target city region to a similar source city region. A neural network is designed to effectively extract region-level representation for spatio-temporal prediction. Finally, an optimization algorithm is proposed to transfer learned features from the source city to the target city with the region matching function. Using crowd flow prediction as a demonstration experiment, we verify the effectiveness of RegionTrans