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Homomorphic Encryption (HE) is a promising technology to protect clients’ data privacy for Machine Learning as a Service (MLaaS) on public clouds. However, HE operations can be orders of magnitude slower than their counterparts for plaintexts and thus result in prohibitively high inference latency, seriously hindering the practicality of HE. In this paper, we propose a HE-based fast neural network (NN) inference framework–SpENCNN built upon the co-design of HE operation-aware model sparsity and the single-instruction-multiple-data (SIMD)-friendly data packing, to improve NN inference latency. In particular, we first develop an encryption-aware HE-group convolution technique that can partition channels among different groups based on the data size and ciphertext size, and then encode them into the same ciphertext by novel group-interleaved encoding, so as to dramatically reduce the number of bottlenecked operations in HE convolution. We further tailor a HE-friendly sub-block weight pruning to reduce the costly HE-based convolution operation. Our experiments show that SpENCNN can achieve overall speedups of 8.37×, 12.11×, 19.26×, and 1.87× for LeNet, VGG-5, HEFNet, and ResNet-20 respectively, with negligible accuracy loss. Our code is publicly available at https://github.com/ranran0523/SPECNN.