microRNAs play an important role in cancer metabolisms. miRNA-181a-5p has decreased expression, particularly in non small cell lung cancer tissues and mesenchymal like lung cancer cells. Epithelial-mesenchymal transition mechanisms and cancer metabolism are regulated by the same signaling pathway. Functional analysis was performed to identify the functional role of miRNA-181a-5p in cancer metabolism and to find the target gene. To define the role of miRNA-181a-5p in cancer metabolism, we performed LDH assay, glucose uptake assay, Oil Red O staining, and mitochondrial ATP synthase inhibitor assay. The target gene of miRNA-181a-5p was determined by luciferase reporter assay, qRT-PCR, and western blot analyses. The Functional effect of miRNA-181a-5p on cancer metastasis was measured by migration and invasion assays. Experimental results showed that overexpression of miRNA-181a-5p reduced aerobic glycolysis and adipocytes and decreased cancer cell invasion and migration. Expression of SIRT1 and ACSL4 was reduced by the binding of miRNA-181a-5p to the 3’-UTR. These results suggest that miRNA-181a-5p might participate in the reprogramming of cancer metabolism.