The transcription factor STAT4 has been implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and diabetes mellitus. Here, we report p-biaryl phosphates and phosphonates as the first small-molecule inhibitors of STAT4. The most potent p-biaryl phosphate inhibited the protein-protein interaction domain of STAT4, the SH2 domain, with submicromolar potency (K