Lung cancer is the leading cause of cancer deaths worldwide, many miRNAs play critical role in lung cancer initiation and progression. Here, we demonstrated that miR-1254 was upregulated in lung cancer tissues and cells. miR-1254 overexpression promoted lung cancer cell proliferation determined by MTT assay, colony formation assay, soft agar growth ability assay and BrdU incorporation assay, miR-1254 knockdown suppressed lung cancer cell proliferation. Mechanism analysis revealed that Wnt/β-catenin pathway antagonist secreted frizzled related protein 1 (SFRP1) was its target, its expression was opposite to SFRP1 level, and directly bound to the 3′UTR of SFRP1. Double knockdown of miR-1254 and SFRP1 promoted lung cancer cell proliferation, suggesting miR-1254 promoted lung cancer cell proliferation by targeting SFRP1.