This book constitutes the Second International Challenge on Kidney and Kidney Tumor Segmentation, KiTS 2021, which was held in conjunction with the 24th International Conference on Medical Image Computing and Computer-Assisted Intervention, MICCAI 2021. The challenge took place virtually on September 27, 2021, due to the COVID-19 pandemic. The 21 contributions presented were carefully reviewed and selected from 29 submissions. This challenge aims to develop the best system for automatic semantic segmentation of renal tumors and surrounding anatomy.