Tumor progression has an intimate link with tumor microenvironment inflammation. Chemo-therapy often induces cellular inflammation which is a risk factor of tumor invasion and metastasis. Molecules that reduce the tumor-associated inflammation could play pivotal roles in controlling tumor progression. Prostasin is an epithelial glycosylphosphatidylinositol-anchored membrane serine protease. Prostasin has been implicated for its mechanistic roles in maintaining the integrity of the epithelium via regulating the tight junctions at the cell-cell contacts, in taming innate epithelial inflammation via regulating inflammatory mediators’ expression including inducible nitric oxide synthase and cyclooxygenase-2, and in inhibiting tumor cell invasion and metastasis. Our research is focused on elucidating the mechanisms of prostasin’s roles in inflammation-associated cancer development and progression. We aim to investigate if prostasin can be used as an agent for therapeutic intervention to decrease the incidence and spread of cancers by controlling the status of the tumor-associated inflammation; and to increase chemotherapy efficacy.