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RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes plays a role in cancer progression. However, its clinical significance in metastatic colorectal cancer (CRC) remains unclear. This study aimed to evaluate whether ADAR1 expression predicts prognosis and treatment response in colorectal cancer (CRC) with synchronous liver metastasis. This study included 40 patients with stage IV CRC and synchronous liver metastases. ADAR1 expression in tumor tissues was evaluated using immunohistochemistry. Expression levels were quantified using the immunoreactive score, and associations with clinicopathological features, overall survival (OS), and chemotherapy response were examined. High ADAR1 expression was significantly associated with multiple liver metastases (P = 0.0206), lymph node metastasis (P = 0.0241), and reduced response to chemotherapy (P = 0.0224). Significantly shorter OS was observed in patients with high ADAR1 expression in the nucleus (P = 0.0458). ADAR1 expression was an independent prognostic factor comparable to the presence of extrahepatic metastases. Low ADAR1 expression was correlated with a higher likelihood of achieving a response to chemotherapy. ADAR1 expression can reflect tumor aggressiveness and chemotherapy resistance in patients with CRC and synchronous liver metastasis. ADAR1 has considerable potential as a dual-purpose biomarker for stratifying patients based on prognosis and optimizing treatment intensity.