Steve Rozen's research has ranged over bioinformatics, human genetics & cancer genomics. Rozen founded and, until 2021, directed the Centre for Computational Biology at Duke-NUS in Singapore.

Rozen's laboratory at Duke-NUS worked on bioinformatics and cancer genomics, and was part of a team-science effort in cancer genomics with Patrick Tan and Bin Teh that led to multiple papers, including 5 in Nature Genetics. This research was also recognized by the American Association for Cancer Research (AACR) 2018 Team Science Award to the "Genomic Approaches to Preventing and Treating Asian-Prevalent Cancers Team" for work on aristolochic acid mutagenesis in liver and urinary tract cancers and for genomic studies of biliary tract cancers, lymphomas, and gastric cancers.

Within cancer genomics, the Rozen laboratory also studied alternative splicing, lncRNAs, and use of mutational signatures as tools for studying the molecular epidemiology of cancer. Rozen also created and maintained the widely-used Primer3 software for PCR primer design. Previously, he also worked extensively on identifying mutations in human Y chromosomes and their clinical consequences, as reported in multiple publications in Nature Genetics and Nature.