Objective：To analyze the differential expression profile of microRNAs in murine melanoma B16F0 and B16F10 cells，and to isolate the microRNAs related to the proliferation and metastasis of malignant melanoma. Methods：We verified the difference of B16F10 and B16F0 cell in vivo and in vitro. And then RiboArrayTM miDETECTTM Mouse Array was adopted to compare the microRNAs expressed in murine melanoma B16F0 and B16F10 cells. The differently expressed microRNAs were further confirmed by real time PCR. Results：B16F10 cells had stronger abilities of migration and proliferation in vivo and in vitro. Further more，compared with B16F0 cells，a total number of 38 microRNAs were statically differently expressed in B16F10 cells，with 15 upregulated and 23 downregulated. Consistent with RiboArray results，the expressions of miR-26a-1-3p，miR-28b，miR-29b-3p，and miR-24-2-5p were significantly upregulated and the expressions of miR-763，miR-431-5p，miR-205-5p，and let-7c-2-3p were markedly downregulated revealed by real time PCR. Conclusion：Our findings suggest that the differentially expressed microRNAs were related to the occurrence and development of malignant melanoma，and might serve as novel targets for early diagnosis and treatment of melanoma.