Objective To investigate the levels and clinical significance of serum microRNA （miR）-651 and miR-630 in patients with cervical cancer. Methods From June 2017 to May 2020， 108 cervical cancer patients accepted by our hospital were collected as the cervical cancer group. Meantime， 100 cervical intraepithelial neoplasia （CIN） patients treated in our hospital were regarded as the CIN group， and 110 healthy individuals who underwent physical examination were regarded as the control group. Real-time fluorescence quantitative PCR （qRT-PCR） was applied to detect serum levels of miR-651 and miR-630， while analyzing the relationship between serum miR-651 and miR-630 as well as clinical features and prognosis of patients. Results The serum levels of miR-651 and miR-630 in the cervical cancer group and CIN group were obviously lower than those in the control group （P<0.05）， while the serum levels of miR-651 and miR-630 in the cervical cancer group were obviously lower than those in the CIN group （P < 0.05）. The expression levels of serum miR-651 and miR-630 were positively correlated （r = 0.542， P < 0.05）. The serum levels of miR-651 and miR-630 were related to HPV infection， differentiation， lymph node metastasis， and FIGO staging （P < 0.05）. The overall survival rate of patients with low levels of miR-651 and miR-630 was lower than that of patients with high levels. Cox regression analysis showed that， HPV infection， degree of differentiation， lymph node metastasis， FIGO staging， miR-651， and miR-630 were all influencing factors for the prognosis of cervical cancer patients （P < 0.05）. Conclusion The serum levels of miR-651 and miR-630 in cervical cancer patients decrease， which are related to HPV infection， differentiation， lymph node metastasis， FIGO staging， and prognosis.