This book constitutes the refereed proceedings of the 12th International Conference on High-Performance Computing Systems and Technologies in Scientific Research, Automation of Control and Production, HPCST 2022, held in Barnaul, Russia, during May 20-21, 2022. The 23 full papers included in this book were carefully reviewed and selected from 116 submissions. They were organized in topical sections as follows: hardware for high-performance computing and signal processing; information technologies and computer simulation of physical phenomena; computing technologies in data analysis and decision making; and computing technologies in information security applications.