Abstract: ObjectiveTo invasigate the efficacy and side effects differences between modified FOLFOX chrono-chemotherapy with oxaliplatin (L-OHP) combined with 5-fluorouracil (5-Fu) and folinic acid (LV) and standard FOLFOX4 chemotherapy with L-OHP, 5-Fu and LV inadvanced gastrointestinal cancer. MethodsOne hundred and eighty-three patients with advanced gastrointestinal cancer were randomly divided into two groups:chrono-chemotherapy group and conventional -chemotherapy group.Ninety-two patients in chrono-chemotherapy group was infused L-OHP 85～100 mg/m2 from 14:00 to 18:00 (day 1), with the highest plasma drug level at 16:00; LV 200mg/m2 and 5-Fu 1000mg/m2 were administered from 22:00 to 10:00 (day 1~2), with the highest plasma drug level at 4:00 in the morning, using a sinusoidal infusion pump. 91 cases in conventional-chemotherapy group were given standard FOLFOX4 conventional chemotherapy: L-OHP 85～100mg/m2 was infused for 2 hours (day 1); LV 200mg/m2 for 2 hours (day 1~2); 5-FU 400mg/m² was intravenously injected (day 1~2) and 600mg/m2 infused continuously for 22 hours(day 1~2). L-OHP was administrated at normal working time, followed by LV, and then 5-Fu. Chemotherapy was given repeatedly every 30 days for at least 2 cycles. Result The effective rate in chrono-chemotherapy group was 65.2%, and the KPS score increased by 18.7, which were higher than those of Conventional chemotherapy group (P<0.05). The occurrence of adverse effects was obviously lower than that of conventional chemotherapy group (P<0.05). ConclusionCompared with the conventional chemotherapy regime，modified FOLFOX chrono-chemotherapy had a higher effective rate, lower occurrence of adverse effects and better tolerability, which deserves the clinical expansion.