Hepatocellular carcinoma (HCC) is a global public health concern. Current diagnostic methods show poor performance in early-stage HCC detection. Accumulating evidences revealed the great potential of microRNAs (miRNAs) as noninvasive biomarkers in HCC detection. In this study, we examined the diagnostic performance of serum miR-10b, miR-106b, and miR-181a for HCC screening in China. Furthermore, a systematic review of previous related studies was conducted to confirm our results. One hundred eight participants including 27 HCC patients, 31 chronic liver disease (CLD) patients, and 50 healthy people were recruited in this study. Blood specimen was drawn from each participant to extract serum miRNAs. Statistical analyses were performed to assess the 3 miRNAs levels in HCC, CLD patients, and normal controls. A meta-analysis was conducted to further assess the diagnostic value of miRNAs in HCC detection based on previous studies. All these miRNAs (miR-10b, miR-181a, miR-106b) could well discriminate HCC patients from normal controls, with area under the receiver-operating characteristic curve (AUC) values of 0.85 (95% confidence interval [CI]: 0.76-0.94), 0.82 (95% CI: 0.72-0.91), and 0.89 (95% CI: 0.81-0.97), respectively. In addition, these miRNAs could distinguish HCC cases from CLD controls with a medium accuracy. However, the ability of these miRNAs in differentiating CLD patients from normal controls was not satisfactory. Panel of these miRNAs displayed a better performance compared with single miRNA assay, with AUC values of 0.94 (95% CI: 0.89-0.99) in discriminating HCC patients from normal controls and 0.91 (95% CI: 0.80-0.97) in discriminating HCC patients from CLD controls. Results of meta-analysis of previous studies combined with the current study suggested that circulating miRNAs could well differentiate HCC from normal controls, with AUC values of 0.86 (95% CI: 0.82-0.89) for single miRNA assay and 0.94 (95% CI: 0.91-0.96) for miRNA panel assay. Serum miR-10b, miR-106b, and miR-181a have great potential to serve as accurate and noninvasive biomarkers for HCC preliminary screening. Meta-analysis of previous studies combined with current study further confirmed that circulating miRNAs could play an important role in HCC detection. Further large-scale studies are needed to confirm the clinical significance of circulating miRNAs in HCC screening.