OBJECTIVE: To investigate whether miR-let-7c-5p inhibits invasion and migration of bladder cancer cells by regulating HMGA2. METHODS: We used bioinformatics methods to determine the key genes of miR-let-7c-5p. RT-qPCR and Western blotting were used to detect the expressions of miR-let-7c-5p mRNA and HMGA2 protein in bladder cancer and adjacent tissues. With human normal bladder SV-HUC-1 cells as the control, we detected the expression levels of miR-let-7c-5p mRNA and HMGA2 protein in bladder cancer cell lines T24, UM-UC-3 and 5637 with RT-qPCR and Western blotting. We observed the effects of miR-let-7c-5p upregulation (by transfection with a miR-let-7c-5p mimic), miR-let-7c-5p downregulation (using a miR-let-7c-5p inhibitor), and knockdown of both HMGA2 and miR-let-7c-5p on invasion, migration and expressions of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, vimentin, and Snail) in UM-UC-3 cells. Dual luciferase assay, RT-qPCR and Western blotting were used to verify the targeting relationship between miR-let-7c-5p and HMGA2. RESULTS: HMGA2 was identified as one of the target genes of miR-let-7c-5p. Compared with the adjacent tissues, bladder cancer tissues showed a significantly decreased expression of miR-let-7c-5p and an increased expression of HMGA2 protein ( < 0.05). In UM-UC-3 cells, the expression of miR-let-7c-5p was significantly reduced and that of HMGA2 was significantly increased as compared with those in SV-HUC-1 cells (=0.001). Up-regulating miR-let-7c-5p expression significantly lowered the invasion and migration abilities of UM-UC-3 cells, and down-regulating miR-let-7c-5p expression obviously promoted the invasion and migration of UM-UC-3 cells ( < 0.05). Knockdown of both miR-let-7c-5p and HMGA2 expression significantly lowered the invasion and migration ( < 0.05) and inhibited the expressions of EMT-related proteins of UM-UC-3 cells ( < 0.05). CONCLUSION: miR-let-7c-5p inhibits EMT of bladder cancer UM-UC-3 cells by targeting HMGA2, thereby inhibiting the cell invasion and migration.