This book constitutes the refereed proceedings of the Second International Conference on Artificial Intelligence in HCI, AI-HCI 2021, which was held as part of HCI International 2021 and took place virtually during July 24-29, 2021. The total of 1276 papers and 241 posters included in the 39 HCII 2021 proceedings volumes was carefully reviewed and selected from 5222 submissions. The papers included in this volume were organized in topical sections as follows: Ethics, trust and explainability; human-centered AI; AI applications in HCI; and AI applications in smart environments.