Abstract: Objective To investigate the expression and significance of miR-381 in serum and tissues of patients with cervical squamous cell carcinoma.Methods From June 2013 to June 2018, 50 patients with cervical squamous cell carcinoma and 50 patients with cervical intraepithelial neoplasia grade 3 (CIN3) admitted to our hospital were selected as subjects. Another 50 patients who underwent hysterectomy in our hospital for uterine fibroids were included in the control group. The expression levels of miR-381 in serum samples and tissue samples were detected by RT-PCR, and the correlation between miR-381 expression and clinicopathological features of cervical squamous cell carcinoma was analyzed.Results The relative expression of miR-381 in serum and tissues of patients with cervical squamous cell carcinoma and CIN3 was significantly lower than that of the control group, and the difference was statistically significant (P<0.05). The relative expression of miR-381 in serum and tissues of patients with cervical squamous cell carcinoma was significantly lower than that of CIN3, and the difference was statistically significant (P<0.05). The expression of miR-381 in serum and tissues of patients with cervical squamous cell carcinoma was correlated with pathological grade, cervical interstitial infiltration and pelvic lymph node metastasis (P<0.05), and there was no significant correlation with patient age and FIGO stage (P>0.05). The area under the ROC curve of the diagnostic potency of miR-381 in serum of cervical squamous cell carcinoma was 0.821 (95%CI: 0.597-1.042). The diagnostic sensitivity was 92.07%, and the specificity was 79. 42%. The area under the ROC curve of the diagnostic efficiency of miR-381 in tissues of cervical squamous cell carcinoma was 0.893 (95%CI: 0.704-1.625). The diagnostic sensitivity was 95.82%, and the specificity was 83.46%.Conclusions miR-381 shows low expression in serum and tissues of patients with cervical squamous cell carcinoma, and its expression level is correlated with the occurrence and development of cervical squamous cell carcinoma. miR-381 may be a potential marker for the specific diagnosis of cervical squamous cell carcinoma.