This book constitutes the proceedings of the 22nd International Conference on Information Security, ISC 2019, held in New York City, NY, USA, in September 2019. The 23 full papers presented in this volume were carefully reviewed and selected from 86 submissions. The papers were organized in topical sections named: Attacks and Cryptanalysis; Crypto I: Secure Computation and Storage; Machine Learning and Security; Crypto II: Zero-Knowledge Proofs; Defenses; Web Security; Side Channels; Malware Analysis; Crypto III: Signatures and Authentication.