The explosive growth and increasing sophistication of Android malware call for new defensive techniques that are capable of protecting mobile users against novel threats. In this paper, we first extract the runtime Application Programming Interface (API) call sequences from Android apps, and then analyze higher-level semantic relations within the ecosystem to comprehensively characterize the apps. To model different types of entities (i.e., app, API, IMEI, signature, affiliation) and the rich semantic relations among them, we then construct a structural heterogeneous information network (HIN) and present meta-path based approach to depict the relatedness over apps. To efficiently classify nodes (e.g., apps) in the constructed HIN, we propose the HinLearning method to first obtain in-sample node embeddings and then learn representations of out-of-sample nodes without rerunning/adjusting HIN embeddings at the first attempt. Afterwards, we design a deep neural network (DNN) classifier taking the learned HIN representations as inputs for Android malware detection. A comprehensive experimental study on the large-scale real sample collections from Tencent Security Lab is performed to compare various baselines. Promising experimental results demonstrate that our developed system AiDroid which integrates our proposed method outperforms others in real-time Android malware detection. AiDroid has already been incorporated into Tencent Mobile Security product that serves millions of users worldwide.