Abstract: Objective To explore the expression of Cullin 4B （CUL4B） in non-small cell lung cancer （NSCLC） and its effect on NSCLC cell function. Methods The expression of CUL4B was detected by immunohistochemistry and quantitative realtime polymerase chain reaction （qPCR） in 77 cases of NSCLC tissues and 42 cases of normal tissues adjacent to cancer. The qPCR was used to detect the mRNA level of CUL4B in common NSCLC cell lines， including H358， H460， H1299， A549 and SK-MES-1. The highest expression of the cell lines were transfected with siRNA CUL4B （CUL4B interference group） and CUL4B negative control siRNA （negative control group）， respectively. Transfection efficiency was verified by qPCR. The effect of interfering CUL4B expression on the cell proliferation at 24， 48， 72， 96 h was detected by MTT method. Flow cytometry and Transwell assay were used to detect the effect of CUL4B expression on cell apoptosis and invasion at 48 h. Results The high expression rates of CUL4B protein in NSCLC tissues and adjacent normal tissues were 636% （49/77） and 381% （16/42）， and the difference was statistically significant （P<0.05）. CUL4B expression was related to tumor diameter， lymph node metastasis and clinical stage （P<0.05）， but not related to gender， age， pathological type and histological grade （P>0.05）. The relative level of mRNA CUL4B in NSCLC tissue was 2.713±0.246， and interfering CUL4B expression of NSCLC cell， proliferation ability was significantly decreased， cell apoptosis increased and the invasion and metastasis ability decreased. Conclusion CUL4B protein expression was significantly increased in NSCLC tissues and cell lines， and was related to lymph node metastasis， clinical stage and cell differentiation. Silencing CUL4B can affect the proliferation， apoptosis and metastasis of NSCLC cells.