Significance The tumor suppressor syndrome tuberous sclerosis complex (TSC) affects 1:10,000 live births. We discovered that the inflammatory cytokine Interleukin-6 (IL-6) promotes the proliferation and migration of TSC2-deficient cells in part through the regulation of PSAT1 and de novo serine biosynthesis. Importantly, IL-6 neutralizing antibody treatments reduced renal cyst and cystadenoma formation in Tsc2 ^+/− mice. This study highlights a therapeutically targetable vulnerability of TSC, which may have broad clinical application to mTORC1-activated tumors.