This book constitutes the refereed proceedings of the 27th International Symposium on String Processing and Information Retrieval, SPIRE 2021, held in Lille, France, in October 2021.

The 14 full papers and 4 short papers presented together with 2 invited papers in this volume were carefully reviewed and selected from 30 submissions. They cover topics such as: data structures; algorithms; information retrieval; compression; combinatorics on words; and computational biology.

The symposium was held virtually.