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Photodynamic therapy (PDT) provides apparent survival benefits for unresectable cholangiocarcinoma patients. the insufficient sensitivity of cancer cell to PDT treatment limits the clinical application. In this study, according to the GEO datasets, WNT7B expression was decreased by PDT treatment in cholangiocarcinoma samples. In cholangiocarcinoma cells, PDT treatment inhibited Wnt signaling, suppressed cell viability, and enhanced cell apoptosis. Within cholangiocarcinoma cells, PDT treatment induced p53 and miR-34a-5p expression. Under PDT treatment, p53 knockdown downregulated miR-34a-5p expression, whereas the inhibition effect of p53 knockdown on miR-34a-5p could be partially attenuated by agomir-34a-5p. p53 knockdown enhanced cell viability and suppressed cell apoptosis, whereas miR-34a-5p overexpression exerted opposite effects; miR-34a-5p overexpression partially attenuated p53 knockdown effects on PDT-treated cholangiocarcinoma cells. miR-34a-5p directly targeted WNT7B and inhibited WNT7B expression. Under PDT treatment, WNT7B knockdown inhibited the Wnt signaling and cell viability, and promoted cell apoptosis, while miR-34a-5p suppression showed the opposite trends; WNT7B knockdown partially attenuated miR-34a-5p inhibition effects on PDT-treated cholangiocarcinoma cells. In conclusion, PDT treatment induces p53-induced miR-34a transactivation to inhibit cholangiocarcinoma cell proliferation; the miR-34a-5p/WNT7B axis and Wnt signaling are involved.