This study aimed to analyze the expression, clinical significance of cyclin G2 (CCNG2) in esophageal carcinoma, and the biological effect in its cell line by CCNG2 overexpression. Immunohistochemistry and western blot were used to analyze CCNG2 protein expression in 73 cases of esophageal cancer and normal tissues to study the relationship between CCNG2 expression and clinical factors. CCNG2 lentiviral vector and empty vector were respectively transfected into esophageal cancer Eca-109 cell line. Reverse transcription-polymerase chain reaction and western blot were used to detect the mRNA level and protein of CCNG2. MTT assay and cell cycle were also conducted as to the influence of the upregulated expression of CCNG2 that might be found on Eca-109 cell's biological effect. Immunohistochemistry: The level of CCNG2 protein expression was found to be significantly lower in esophageal cancer tissue than normal tissues (P < 0.05). Western blot: The relative amount of CCNG2 protein in esophageal cancer tissue was respectively found to be significantly lower than in normal tissues (P < 0.05). The level of CCNG2 protein expression was not correlated with gender, age, and tumor size (P > 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grades (P < 0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time by Kaplan-Meier analysis. The result of the biological function showed that Eca-109 cell-transfected CCNG2 had a lower survival fraction, more percentage of the G0/G1 phases (P < 0.05), and lower cyclin-dependent kinase 2 (CDK2) protein expression. CCNG2 expression decreased in esophageal cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator to esophageal cancer cell by promoting degradation of CDK2.