Objective:To investigate the expression and clinical significance of Casitas B-lineage lymphoma(Cbl)protein family in cervical squamous cell carcinoma(CSCC). Methods:Immunohistochemistry was used to detect the expression of c-Cbl,Cbl-b,and Cbl-c in 114 cases of CSCC. The correlations between c-Cbl,Cbl-b,and Cbl-c expression and clinicopathological characteristics,disease free survival(DFS)and overall survival(OS)were analyzed. Results:Of the 114 CSCC patients,87 had high c-Cbl expression and 27 had low c-Cbl expression;69 had high Cbl-b expression and 45 had low Cbl-b expression;55 had high Cbl-c expression and 59 had low Cbl-c expression. The histochemistry score(H - score)of c -Cbl in CSCC tissues and the adjacent normal tissues was 143.80 ± 8.76 and 95.13 ± 6.54,respectively. c-Cbl expression was increased in CSCC compared with the adjacent normal tissues(P < 0.001). The H-score of Cbl-b in CSCC tissues and the adjacent normal tissues was 83.95 ± 5.28 and 93.54 ± 3.91,respectively. There was no significant difference in Cbl-b expression between CSCC tissues and the adjacent normal tissues(P=0.146). The H-score of Cbl-c in CSCC tissues and the adjacent normal tissues was 83.62 ± 6.34 and 36.54 ± 4.64,respectively. Cbl-c expression was increased in CSCC compared with the adjacent normal tissues(P < 0.001). c-Cbl expression was higher in highly to moderately differentiated tumors and tumors with a maximum diameter less than 4 cm(both P < 0.05),but it was not related to the patient’s age,vascular invasion,depth of invasion, lymph node metastasis and FIGO stage(all P >0.05). Cbl - b expression was higher in patients with invasion depth > 2/3 of fibromuscular layer(P=0.045),but it was not related to patient’s age,vascular invasion,tumor differentiation,maximum tumor diameter,lymph node metastasis and FIGO stage(all P > 0.05). Cbl-c expression was higher in poorly differentiated tumors(P=0.012), but it was not related to patient’s age,vascular invasion,depth of invasion,maximum tumor diameter,lymph node metastasis and FIGO stage(all P > 0.05). Kaplan - Meier survival analysis showed that patients with high c - Cbl expression had prolonged DFS and OS compared with those with low c-Cbl protein expression(both P < 0.05). However,the expression levels of Cbl-b and Cbl-c were not related to DFS and OS(P > 0.05). Cox univariate and multivariate analysis showed that c - Cbl expression was an independent prognostic factor for DFS(P=0.042). c -Cbl was a factor affecting OS,but not an independent prognostic factor for OS in CSCC(P= 0.096). Conclusion:Patients with high c -Cbl expression have prolonged DFS and OS compared with those with low c -Cbl protein expression. c-Cbl expression is an independent prognostic factor for DFS,but not an independent prognostic factor for OS in CSCC. The expression levels of Cbl-b and Cbl-c are not related to DFS and OS in CSCC. Detection of the expression status of c-Cbl may provide a reference for predicting the prognosis of CSCC patients.