Recently, we have been seeing emerging applications of non-invasive approaches using serum biomarkers including miRnA and proteins in detection of multiple cancers. currently, majority of these methods only use solitary type of biomarkers, which often lead to non-satisfactory sensitivity and specificity in clinical applications. To this end, we established a unique biomarker panel in this study, which determined both squamous cell carcinoma antigen (SCC Ag) degree and miRNA-29a, miRNA-25, miRNA-486-5p levels in blood for detection of early-stage cervical cancer. We designed our study with two phases: a biomarker discovery phase, followed by an independent validation phase. in total of 140 early-stage cervical cancer patients (i.e., AJCC stage I and II) and 140 healthy controls recruited in the biomarker discovery phase, we achieved sensitivity of 88.6% and specificity of 92.9%. To further assess the predictive power of our panel, we used it to an independent patient cohort that consisted of 60 early-stage cervical cancer individuals as well as 60 healthy controls, and successfully achieved both high sensitivity (80.0%) and high specificity (96.7%). Our study indicated combining analyses of multiple serum biomarkers could improve the accuracy of non-invasive detection of early-stage cervical cancer, and potentially serve as a new liquid biopsy approach for detecting early-stage cervical cancer. For women worldwide in the world, cervical cancer, which is ranked as the fourth most frequently occurred cancer 1 , contributed for 6.6% of the total cases of cancer and 7.5% of the total cancer fatalities of women in 2018 1. Additionally, in women of reproductive age, cervical cancer is the major cause 2-4. The transition to invasive cervical cancer from normal epithelium can take more than a decade 5. In the early stage of Ib and II, the overall survival rate of cervical cancer is 70-90%, but this rate significantly goes down to 15% in the late stage of IVa 6. The main reason of the high death rate of cervical cancer is that its asymptomatic and non-specific nature in the early stages makes early detection extremely difficult 7. If early detection of cervical cancer is achieved, there are various treatment options readily available, which make cervical cancer curable. Currently, Papanicolaou test (Pap smear) and colposcopy are the most common methods for cervical cancer detection. For pap smear screening, it had specificity of 98%, but a sensitivity of 51% 8. Also, Pap smear is not very effective at identifying adenocarcinoma, or cervical carcinoma in situ. For certain early-stage cervical cancer, colposcopy and cervical biopsy may be able to recognize it, but these procedures are invasive for patients, and could delay treatment and generate extra costs and risks 9. Serum tumor biomarkers such as Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC Ag) as well as CA19-9 have been frequently used for detecting and monitoring cervical cancer, because they can be measured non-invasively in blood samples 10-1...