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