Plasma leakage through capillary venules is a common response to tissue injury, for example, induced by tumors. It was recently reported that kinins, the short-lived peptides released from blood-borne kininogens, enhance tissue invasion of prostate cancer cells in vitro through the signaling of G-protein coupled kinin receptors. Here we investigated if activation of kinin receptors of PC3 and DU-145, i.e., prostate cancer cell lines respectively expressing kinin B₁ receptor (B₁R) or B₁R/B₂R, may upregulate secretion of lysosomal cysteine proteinases (CPs). We show that both the B₂R agonist bradykinin and desArg⁹-Bradykinin induced [Ca²⁺]_i transients in DU145 cells while desArg⁹-Bradykinin elicited  [Ca²⁺]_i exclusively through B₁R. We then asked if the [Ca²⁺]_i responses elicited through B₂R or B₁R were coupled to upregulated secretion of lysosomal cysteine proteases (CPs). Indeed, the levels of enzymatically active CPs secreted by DU145 or PC3 cultures raised sharply, reaching plateau within 20 min of stimulation. The upregulated secretion of CPs was cancelled upon addition of the specific B₂R or B₁R, by the Ca²⁺ chelator BAPTA-AM or by depletion of [Ca²⁺]_i  stores by thapsigargin.  Notably, the soluble CP inhibitor L-trans-epoxysuccinyl-leucylamido-(4-guanidino)butane (E-64) blocked kinin-driven enhanced cell migration and invasion of Matrigel^® coated membranes by both DU145 and PC3.  We propose that triggering of kinin receptors stimulate exocytosis of lysosomal CPs that contribute to prostate cancer migration and tissue invasion.