Introduction: This study aimed to explore the effects of miR-345-5p on papillary thyroid carcinoma (PTC) and uncover the possible mechanisms. Material and methods: MiR-345-5p and SETD7 mRNA levels were analyzed by quantitative real-time PCR and SETD7 protein level was measured by Western blot. The viability, colony formation ability and apoptosis of PTC cells were measured with CCK-8, soft agar colony formation and flow cytometry assay, respectively. Luciferase reporter assay was used to identify miR-345-5p's target. Results: Compared to neighboring normal tissues, there was lower miR-345-5p expression and higher SETD7 expression in PTC tissues. Moreover, Spearman's correlation analysis indicated that there was a negative correlation between miR-345-5p and SETD7 expression in PTC tissues. MiR-345-5p mimics inhibited the viability and colony formation of TPC1 and B-CPAP cells and promoted apoptosis, whereas anti-miR-345-5p promoted PTC cell proliferation and inhibited apoptosis. SETD7 was confirmed to be a direct target of miR-345-5p through target scan analysis and luciferase reporter assay. Additionally, overexpression of SETD7 promoted the viability and colony formation of TPC1 and B-CPAP cells and inhibited apoptosis, whereas downregulation of SETD7 by shRNAs had opposite effects on PTC cells. Furthermore, overexpression of SETD7 attenuated the miR-345-5p induced anti-tumor effects on PTC cells. Conclusions: MiR-345-5p exhibited suppressive effects on PTC via targeting SETD7.