Early detection of ovarian cancer, the most lethal type of gynecologic cancer, can dramatically improve the efficacy of available treatment strategies. However, few screening tools exist for rapidly and effectively diagnosing ovarian cancer in early stages. Here, we present a facile "lock-key" strategy, based on rapid, specific detection.of plasma lysophosphatidic acid (LPA, an early stage biomarker) with polydiacetyleoes (PDAs)-based probe, for the early diagnosis of ovarian cancer. This strategy relies on specifically inserting LPA "key" into the PDAs "lock" through The synergistic electrostatic and hydrophobic interactions between them, leading to conformation transition of the PDA backbone- with a concomitant-blue-to-red color', change. The detailed mechanism underlying the high selectivity of PDAs toward LPA-is revealed by comprehensive theoretical calculation and experiments. Moreover; the level of LPA can be quantified in plasriia samples from both mouse xenograft tumor models and patients with ovarian cancer. Impressively, this approach can be introduced into a portable point-of-care device to successfully distinguish the blood samples of patients with ovarian cancer from those of healthy people, with 100% accuracy. This work provides a valuable portable tool for early diagnosis of ovarian cancer and thus holds a great promise to dramatically improve the overall survival.