In summary, our findings demonstrate that in the nucleus, USP7 negatively regulates DICER at the protein level forming a new regulatory axis, which affects DNA damage repair and then regulates tumour growth, and that MDM2 is a new ubiquitin E3 ligase of DICER, which indirectly mediates the negative regulation of DICER by USP7. Here, USP7 is linked to neoplasm.