Background and Aims Synchronous liver metastasis is an important determinant of treatment strategy and prognosis in patients with colorectal cancer. Identifying patients at high risk of liver metastasis at initial diagnosis may facilitate risk stratification and individualized management. This study aimed to characterize the clinicopathological and molecular features of synchronous colorectal liver metastasis and to identify its independent associated factors.Methods The clinical data from 373 patients with colorectal cancer who were treated at Xiangya Hospital, Central South University, between January 1, 2016 and December 31, 2023, were retrospectively collected. Patients were divided into a liver metastasis group and a non-liver metastasis group according to the presence of liver metastasis at initial diagnosis. Clinicopathologic characteristics, tumor markers, and molecular features, including KRAS, NRAS, BRAF^V600E, and microsatellite instability (MSI) status, were compared between the two groups. Firth penalized Logistic regression was performed to identify independent factors associated with synchronous liver metastasis.Results Among the 373 patients, 92 (24.66%) had synchronous liver metastasis. Univariate analysis showed that tumor location, lymph node metastasis, extrahepatic distant metastasis, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and MSI status were associated with synchronous liver metastasis (all P<0.05). Multivariate Firth regression analysis identified lymph node metastasis (OR=2.828, 95% CI=1.346-6.489, P=0.005), extrahepatic distant metastasis (OR=2.243, 95% CI=1.176-4.279, P=0.014), and positive CEA (OR=4.519, 95% CI=2.537-8.262, P<0.001) as independent risk factors. Rectal primary tumor (OR=0.491, 95% CI=0.278-0.852, P=0.011) and MSI (OR=0.112, 95% CI=0.001-0.917, P=0.039) were independently associated with a lower risk of synchronous liver metastasis.Conclusion Tumor location lymph node metastasis, extrahepatic distant metastasis, and positive CEA were independently associated with an increased risk of synchronous liver metastasis, whereas rectal primary tumor and MSI were associated with a lower risk. These clinicopathological and molecular characteristics may help stratify the risk of synchronous liver metastasis in patients with newly diagnosed colorectal cancer and may provide a basis for further hepatic imaging evaluation and individualized management.