Objective To observe the effect of two different chemotherapy regimens, including irinotecan, folinic acid and FU chemotherapy regimen (FOLFIRI) versus folinic acid, FU and oxaliplatin chemotherapy regimen (mFOLFOX6) on nutritional status in patients with advanced colon cancer. Methods A total of 110 patients with advanced colon cancer in Shanxi Cancer Hospital were divided into FOLFIRI (group A) and mFOLFOX6 (group B). To investigate the effect of two different regimens on the patients with advanced colon cancer by toxicity, the traditional methods of nutritional assessment, scored patient-generated subjective global assessment (PG-SGA), nutrition risk screening-2002 (NRS-2002). Shapiro-Wilk was used to detect the normality of small samples, t test was used to analyze measurement data conformed to the normal distribution, Wilcoxon non-parametric test was used to analyze the abnormal distribution data, and enumeration data was detected by using chi-square test. Results The incidence of vomiting, diarrhea and alopecia in group A and group B was respectively 53.8 % (28/52) vs. 29.3 % (17/58), 65.4 % (34/52) vs. 43.1 %(25/58),46.2 %(24/52)vs.20.7 %(12/58)respectively,and there was a significant difference(all P <0.05). The albumin, body mass index, NRS-2002 score, PG-SGA score after chemotherapy were significantly lower than those before chemotherapy in both groups (all P < 0.05). PG-SGA scores after chemotherapy in group A and group B were respectively 7.0 and 5.5 (Z= -2.026, P< 0.05). There were no statistically significant differences between the two groups in the albumin, body mass index, triceps skin fold (TSF), arm muscle weeks diameter(MAMC)and NRS-2002 score(all P >0.05).Conclusions FOLFIRI and mFOLFOX6 scheme can reduce the patient's nutritional status. The probability of gastrointestinal adverse reaction of FOLFIRI regimen is high, which may have an obvious impact on nutritional status of patients compared with mFOLFOX6 scheme.