Efficacy of circadian chronotherapy for liver metastases from colorectal cancer was evaluated. Chronomodulated infusion of anticancer drugs via the hepatic artery(HAI) was applied for patients with marginally resectable or unresectable liver metastases at initial diagnosis. Response rate of chemotherapy and frequency of liver resection after chemotherapy of patients treated with chronomodulated HAI were higher than those treated with flat HAI. Further, combination of chronomodulated regional HAI and systemic chemotherapy was the most effective prehepatectomy chemotherapy for the treatment of patients with advanced colorectal liver metastases. Based on these results, we are now performing phase II non-randomized open labeled trial of chronomodulated HAI with systemic administration of panitumumab for patients with such advanced liver metastases (ccFLAP trial). Circadian chronotherapy is an effective prehepatectomy chemotherapy for the treatment of patients with advanced and aggressive liver metastases from colorectal cancer.