MicroRNAs are a class of short, highly conserved, non-coding RNAs that function as negative posttranscriptional regulators of target genes. Accumulating evidence has shown that miRNAs are aberrantly expressed during the development and/or progression of a variety of human cancers. Roles for miRNAs in the regulation of tumorigenesis via the targeting of important genes within signaling pathways are evident. To date, however, miRNAs that target FHL1 have not been reported. To clarify the mechanism of FHL1 downregulation during tumorogenesis, we assessed the involvement of miRNAs that target the FHL1 promoter. We report that Torin 1 miR-410 is upregulated in colorectal cancer and hepatocarcinoma and that miR-410 can decrease FHL1 protein levels both directly by targeting the FHL1 3’UTR and indirectly by promoting the upregulation of DNA methylases. In particular, miR-410 promotes the binding of DNMT3A to the FHL1 promoter, which leads to the hypermethylation of the FHL1 promoter. The findings here could provide a mechanism for FHL1 down-regulation during tumorigenesis. Consistently, analysis of clinical hepatocarcinoma and colorectal specimens revealed a physiological association between the expression of miR-410, FHL1 and DNMT3A, which implicates miR-410 as a potential oncogenic biomarker that functions by down-regulating FHL1 in these tissues. The findings here within indicate, for the first time, that miR410 may serve as a regulator of FHL1 expression through direct targeting of its 3’UTR and indirect regulation of its methylation in human colorectal cancer and hepatocarcinoma. Recent reports have shown other possible functions of miR-410. miR410 is involved in the regulation of lipoprotein lipase levels, muscle regeneration, and idiopathic pulmonary fibrosis. Also, miR-410 is considered a diagnostic and prognostic biomarker in some diseases. In a study based on plasma samples from 122 women, tumor tissues with a combination of miR-92a/miR-410 or miR-92a/miR-205/miR-410 expression was shown to serve as a noninvasive biomarker for early cancer detection and prognosis. Therefore, there is a precedent for a possible role of miR-410 as a biomarker for malignant diseases. Our results also show that expression is elevated in clinical tissue from colorectal and liver tumors; however, based on our limited sample size, the use of a larger sample size may be required to confirm the potential utility of miR-410 as a biomarker for colorectal and liver tumors. FHL1 is a well known tumor-suppressor gene with no or relatively low expression in tumors. Methylation-silenced mutation is one of the important mechanisms contributing its low-expression. Here, we have shown another new mechanism for silencing of FHL1 expression in tumors: miR-410 not only specifically targets the 39UTR of FHL1, but also promotes DNMT3A binding to the FHL1 promoter, which leads to its hypermethylation in cancer cells, suggesting that the regulation of FHL1 by miR-410 occurs by dual mechanisms. Exogenous miR-410 expression leads to the upregulation of methylases, and both miR-410 and DNMT3A are upregulated.