Chemotherapy plays a crucial role in the treatment of colon cancer, especially in the postoperative adjuvant and metastasis therapy. Recently, the chemotherapy of colon cancer mainly adopts combined chemotherapy and oxaliplatin has been approved as a member of drug combination of metastatic colon cancer. In this scheme, the oxaliplatin declines relatively the side effects and improves the therapeutic effectiveness. Nevertheless, it still exists individual difference of side effects and resistance, which could be relevant to many factors, among which the genetic differences play an essential role. This review reports the recent genetic single nucleotide polymorphisms (SNPs) and their mechanisms that are involved in the toxicity and resistance of oxaliplatin based combination chemotherapy in colon cancer and provides valuable resources for further scientific research and clinical individualized medication.