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CircRNAs can be applied as tumor biomarkers and potential therapeutic targets. Nevertheless, the function of circ_PSD3 in papillary thyroid carcinoma (PTC) has not been thoroughly explored. The current project attempts to analyze it. RT-qPCR was adopted for measuring the expression of circ_PSD3, HMGB3, miR-145-5p as well as miR-338-3p in PTC tissues and cells. Through performing cell counting kit-8 and transwell experiments, the biological effects of circ_PSD3, HMGB3, miR-145-5p and miR-338-3p on PTC cells were detected. Besides, a dual-luciferase reporter gene was employed to identify the underlying mechanism of circ_PSD3. The Western blot analysis assay was utilized to assess the expression levels of molecular marker proteins associated with epithelial-mesenchymal transition. According to the results, the expressions of circ_PSD3 and HMGB3 showed obvious upregulation in PTC tissues, whereas knockdown of circ_PSD3 or HMGB3 notably hindered cell proliferation, migration as well as invasion in PTC. Mechanistically, it could be discovered that miR-145-5p and miR-338-3p served as the targets of circ_PSD3, and HMGB3 was a target of miR-145-5p and miR-338-3p. Moreover, miR-145-5p and miR-338-3p were discovered to play the role of tumor suppressors in PTC. More importantly, the findings showed that cell proliferation, migration, invasion together with EMT processes were attenuated by circ_PSD3 knockdown, but partially counteracted by miR-338-3p (miR-145-5p) inhibitor or HMGB3 overexpression. Based on the obtained data, circ_PSD3 promotes PTC cell proliferation, migration, invasion and EMT by regulating the miR-145-5p/miR-338-3p/HMGB3 axis. The current work revealed the mechanism of action of circ_PSD3 in PTC and may play the role of a new medical target for PTC.