Automated clinical coding (ACC) has emerged as a promising alternative to manual coding. This study proposes a novel human-in-the-loop (HITL) framework, CliniCoCo. Using deep learning capacities, CliniCoCo focuses on how such ACC systems and human coders can work effectively and efficiently together in real-world settings. Specifically, it implements a series of collaborative strategies at annotation, training and user interaction stages. Extensive experiments are conducted using real-world EMR datasets from Chinese hospitals. With automatically optimised annotation workloads, the model can achieve F1 scores around 0.80–0.84. For an EMR with 30% mistaken codes, CliniCoCo can suggest halving the annotations from 3000 admissions with an ignorable 0.01 F1 decrease. In human evaluations, compared to manual coding, CliniCoCo reduces coding time by 40% on average and significantly improves the correction rates on EMR mistakes (e.g., three times better on missing codes). Senior professional coders’ performances can be boosted to more than 0.93 F1 score from 0.72.