MicroRNAs that negatively regulate gene expression have emerged as novel therapeutic tools for cancer treatment. In the present study, we investigated the role of let-7f in non-small cell lung cancer (NSCLC) tumorigenesis and progression. Our results showed that let-7f was down-regulated in NSCLC tissues. Overexpression of let-7f inhibited NSCLC cell proliferation, migration and invasion. Further data demonstrated that TGFBR1 was a direct target of let-7f, and played a crucial role in let-7f mediated suppressive effect on NSCLC cell migration and invasion abilities. In summary, these findings indicated that let-7f acts as a tumor suppressor in NSCLC, and it reduces the cancer cell motility and invasive capacity by targeting TGFBR1, providing a potential anti-cancer drug candidate for NSCLC.