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Background and objective MicroRNAs (miRNAs) regulate a wide range of cancer-associated processes, including cell division, proliferation, cell cycle, apoptosis, angiogenesis, invasion, and metastasis. A microarray was performed to analyze metastasis-related miRNAs with different metastastic potentials and to further elucidate their mechanism in the large-cell lung cancer cell lines. Methods L9981 and NL9980 cells were harvested, and total RNA was extracted for CY3. RNA hybridization was then performed on the chip with marked miRNAs. MiRNAs with significantly different expression were selected through statistical analysis. A real-time polymerase chain reaction (PCR) was employed to validate the results of the microarray, and target genes were predicted using bioinformatics. Results Expressions of 22 miRNAs were significantly different in the L9981/NL9980 cell lines. Compared with the NL9980, 13 miRNAs were upregulated in the L9981 cell lines, whereas 9 miRNAs were downregulated. The result of miR-125a-3p expression based on real-time PCR was consistent with the microarray. Insulin-like growth factor 2 might be a target gene of miR-125a-3p. Conclusion The metastatic miRNA profile in large-cell lung cancer was successfully screened out.