The primary cilium is a cell surface-anchored sensory organelle which expression is lost in hypoxic cancer cells and during mesenchymal stromal cells (MSC) adaptation to low oxygen levels. Since pro-inflammatory cues are among the early events which promote tumor angiogenesis, we tested the inflammatory cytokine tumor necrosis factor (TNF)-α and found that it triggered a dose-dependent loss of the primary cilia in MSC. This loss was independent of IFT88 expression, was abrogated by progranulin, an antagonist of the TNF receptor and required the NF-κB signaling intermediates IκB kinase α, β, and γ, as well as NF-κB p65. These findings strengthen the concept that the primary cilium may serve as a biomarker reflecting the tumor-supporting potential of MSC and their capacity to adapt to hypoxic and pro-inflammatory cues.