Cryoablation and surgery achieve similar removal rates for some colorectal cancer (CRC) liver metastasis removal, and systemic chemotherapy is accepted as the most important approach to improving overall survival (OS) in CRC patients with liver metastases. We aimed to evaluate the potential benefit of cryoablation plus chemotherapy in CRC patients with liver metastases. We retrospectively analyze 63 patients of CRC liver metastasis. There were 32 patients in group A, who have received cryoablation plus chemotherapy, and there were 31 patients in group B, who have received chemotherapy alone. We mainly observe the 2-year survival, the quality of life (QOL), and adverse effects. Patients in group A had a higher 2-year survival rate, better OS, better QOL, and better treatment response than patients in group B. Two-year survival rates were 71.9 and 51.6%,respectively, in group A and group B. The negative conversion rates of carcinoembryonic antigen and carbohydrate antigen 19-9 (CA199) were 57.1 and 61.5%, respectively, in group A, and 22.2 and 30%, respectively, in group B. The tumor shrinkage (a tumor volume reduction of ≥ 30%) rates were 62.5 and 22.6%, respectively, in groups A and B. Performance status remained stable or improved in 16 patients (50%) in group A and eight patients (25.81%) in group B. Cryoablation in combination with chemotherapy may increase the 2-year survival rate and improve QOL in CRC patients with liver metastasis.