Rationale:Many studies have reported radical resection for liver metastasis and the primary tumor could represent an important prognostic factor in patients affected by colorectal liver metastases (CRLM). However, resection of huge liver metastases from colon cancer has been seldom reported.Patient Concerns:A 58-year-old man presented with huge liver metastases from colon cancer. Laboratory tests revealed elevated tumor markers and a wild-type mutation in the K-RAS gene. A computed tomography scan demonstrated unresectable liver masses with a 16.5-cm maximum diameter and intrahepatic duct dilatation due to compression by the liver metastases.Diagnosis:The patient was diagnosed with stage IV descending colon carcinoma with multiple huge hepatic metastases.Interventions:He was administered 3 treatment courses, including 9 cycles of combined chemotherapy with mFOLFOX6 plus cetuximab (mFOLFOX6 + Cet), and the liver masses reduced. After a preoperative assessment by a multidisciplinary team when the 9 cycles of systemic chemotherapy had been completed, the patient underwent hepatectomy, followed 4 months later by a laparoscopic colectomy. We used a reverse strategy (liver-first) for the patient.Outcomes:In this case, liver-first treatment (systemic chemotherapy of mFOLFOX6 + Cet) was an effective treatment for unresectable CRLM. No postoperative complications occurred. The patient continued to receive postoperative chemotherapy (mFOLFOX6 + Cet) at the latest follow-up. During the 17 months of follow-up, tumor recurrence was un-noted.Lessons:Treating colorectal cancer patients with huge hepatic metastases is possible, and surgeons should consider various treatment options in the management of these patients.