Recently, convolutional neural network (CNN) has attracted tremendous attention and has achieved great success in many image processing tasks. In this paper, we focus on CNN technology combined with image restoration to facilitate video coding performance and propose the content-aware CNN based in-loop filtering for high-efficiency video coding (HEVC). In particular, we quantitatively analyze the structure of the proposed CNN model from multiple dimensions to make the model interpretable and optimal for CNN-based loop filtering. More specifically, each coding tree unit (CTU) is treated as an independent region for processing, such that the proposed content-aware multimodel filtering mechanism is realized by the restoration of different regions with different CNN models under the guidance of the discriminative network. To adapt the image content, the discriminative neural network is learned to analyze the content characteristics of each region for the adaptive selection of the deep learning model. The CTU level control is also enabled in the sense of rate-distortion optimization. To learn the CNN model, an iterative training method is proposed by simultaneously labeling filter categories at the CTU level and fine-tuning the CNN model parameters. The CNN based in-loop filter is implemented after sample adaptive offset in HEVC, and extensive experiments show that the proposed approach significantly improves the coding performance and achieves up to 10.0% bit-rate reduction. On average, 4.1%, 6.0%, 4.7%, and 6.0% bit-rate reduction can be obtained under all intra, low delay, low delay P, and random access configurations, respectively.