Colorectal cancer (CRC) is one of most common causes of cancer-related death worldwide. Recent studieshave suggested that microbial and environmental factors including diet and lifestyle can impact on colon cancerdevelopment. Vitamin D deficiency and dysfunction of vitamin D receptor (VDR) also correlate with coloncancer. Moreover, leptin, a 16-kDa polypeptide, participates in the regulation of food intake and is associatedwith other environmental factors affecting colon cancer through the leptin receptor. Altered levels of serum leptinand patterns of expression of its receptor (LPR) may be observed in human colon tumours. Furthermore, thecollected data from in vitro and in vivo studies have indicated that consuming probiotic non-pathogenic lacticacid bacteria have beneficial effects on colon cancer. Probiotics, inflammation and vitamin D/VDR have beencorrelated with leptin and its receptor and are also with colon cancer. Thus, in this paper, we review recentprogress on the roles of probiotic, vitamin D/VDR and leptin/LPR in inflammation and colon cancer.