Steve Rozen's research has ranged over bioinformatics, human genetics & cancer genomics. Rozen founded and directs the Duke-NUS Centre for Computational Biology. The Centre's 5 regular-rank faculty have published > 250 scientific papers since 2013 and the Centre offers a PhD program in bioinformatics.

Rozen's own laboratory focuses on bioinformatics and cancer genomics, and is part of team-science efforts in cancer genomics that have 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 Lab studies alternative splicing, lncRNAs, and use of mutational signatures as tools for studying the molecular epidemiology of cancer. Rozen also created and maintains 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.

The Rozen laboratory also co-led a major study that used machine learning to computationally mine mutation data from almost 24,000 human cancer samples to identify 81 "mutational signatures" that will help reveal the origins and development of various types of cancer (published in Nature, 2020 https://doi.org/10.1038/s41586-020-1943-3).