In the present study, we prepared eighty-five different kinds of lees extracts and their solvent fractions and investigated their anti-proliferative activities against human colorectal cancer HCT116 cells. HCT116 cells were treated with eighty-five solvent fractions of lees extracts and then the cell viability was measured by using MTS assay. Among the treated solvent fractions, three solvent fractions (KSD-E1-3, KSD-E2-3 and KSD-E4-3) were selected based on cell viability assay. In addition, we performed oligo DNA microarray analysis to analyze gene expression changes by treatment of KSD-E1-3 in HCT116 cells. Among the up-regulated genes, we selected 4 genes (NAG-1, ATF3, p21, and DDIT3) and performed RT-PCR using gene specific primers. Among treated solvent fractions, KSD-E1-3 dramatically induced expression of four selected genes. In addition, we investigated whether up-regulation of those genes were dependent on transcription factor p53 presence or not using p53 null HCT116 cells. The results indicate that up-regulation of NAG-1, ATF3, and DDIT3 is not dependent on p53 presence, whereas p21 is dependent on p53 presence. And we prepared additional five sub-fractions from KSD-E1-3 extracts using various organic solvents. We investigated the effects of those fractions on cell viability using HCT116 cells, respectively. Among treated fractions, KSD-E1-3-3 dramatically decreased cell viability and increased expression of anti-proliferative genes such as ATF3, NAG-1, DDIT3 and p21 genes. To confirm RT-PCR data, we performed quantitative real-time PCR using gene specific primers. And we investigated the inhibitory effects of KSD-E1-3-3 on cell migration and invasion, which are two critical cellular processes that are often deregulated during metastasis, using HCT116 cells. And we prepared additional six sub-fractions from KSD-E4-3 extracts using various organic solvents. And, we investigated the effects of those fractions on cell viability and NO production in mouse macrophage RAW264.7 cells. Among treated fractions, KSD-E4-3-2 significantly decreased NO production in LPS-activated RAW264.7 cells without affecting cell viabilities. Also, they reduced the expression of pro-inflammatory genes such as COX-2, iNOS and TNF-alpha. Overall, our results suggest that lees may possess various biological activities such as anti-proliferative and anti-inflammatory activities and can be a novel resource for the development of functional foods and cosmetics which contain anti-proliferative and anti-inflammatory activities.