Lung cancer seriously threatens human health, so it is important to investigate gene expression changes inaffected individuals in comparison with healthy people. Here we compared the gene expression profiles betweensmokers with and without lung cancer. We found that the majority of the expressed genes (threshold was set as0.1 RPKM) were the same in the two samples, with a small portion of the remainder being unique to smokerswith and without lung cancer. Expression distribution patterns showed that most of the genes in smokers withand without lung cancer are expressed at low or moderate levels. We also found that the expression levels ofthe genes in smokers with lung cancer were lower than in smokers without lung cancer in general. Then wedetected 27 differentially expressed genes in smokers with versus without lung cancer, and these differentiallyexpressed genes were foudn to be involved in diverse processes. Our study provided detail expression profilesand expression changes between smokers with and without lung cancer.