Colorectal cancer (CRC) is the third major cause of cancer death globally, with about 694,000 deaths each year. Recent studies have shown that cancer stem cells (CSCs) play an important role in cancer relapse and metastasis. Inhibition of COX-2, Wnt / beta-catenin, HIF-1 alpha, K-Ras, NF-kβ, P53 signaling pathways and activation of TGF-β are amongst proposed strategies against colorectal cancer. Specific markers of CSCs including CD133, CD24, CD29, CD44 and Lgr5 are also of importance in diagnosis and monitoring of the disease. Therefore, the use of nanoparticles can be discussed in two different fields: 1. using nanoparticles in diagnosis and targeting CSCs, 2. targeting the cancer cells directly, where nanoparticles can affect the cell signaling pathways and expression patterns to prevent extension of tumor cells. In addition, nanoparticles can be used as the carriers for anti-cancer drugs and drug delivery, which in turn may enhance effectiveness of treatment. This review covers the novel signaling pathways in colorectal cancer and also gives a brief explanation about the role of some nanostructures that enhance treatment efficiency.