In this study, we investigated specific molecular functions and roles of NAP1L1 in glioma cells, thereby providing evidence that NAP1L1 could promote cell proliferation and chemoresistance in glioma cells by interacting with HDGF and subsequently, activating c-Jun to induce CCND1/CDK4/CDK6 expressions. The gene discussed is CDK6; the disease is central nervous system cancer.