In summary, compared to knockdown of miR-21 or CXCR4, double-targeted knockdown of miR-21 and CXCR4 could more effectively inhibit the proliferation, migration, invasion, and growth of transplanted tumor and promote cell apoptosis, which were involved in the PI3K/AKT and Raf/MEK/ERK signaling pathways. Here, CXCR4 is linked to neoplasm.