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. This evidence concerns the gene NAP1L1 and central nervous system cancer.