The study aimed to evaluate the efficacy of the combination of CPP-ACP and fluorides compared with fluorides monotherapy on patients with early caries lesions. The Medline, Embase and Cochrane databases up to August 2017 were scanned, with no restrictions. Studies satisfied the guideline of randomised controlled trials (RCTs), the patients with early caries lesions and data considering the efficacy of fluorides and CPP-ACP versus fluorides alone were selected. There was no language restriction during the literature search process, however, only papers in English or Chinese were included during the selection process. Outcome variables include laser fluorescence, quantitative light-induced fluorescence, lesion area and visual inspection scores. Mean differences were calculated during the data extraction process. Ten studies including 559 patients were selected in the meta-analysis. Fluorides combined with CPP-ACP achieved the same efficacy for early caries lesions on smooth surfaces compared with fluorides monotherapy (mean difference: -13.90, 95% confidence interval: -39.25, 11.46, P = 0.28), and the combination treatment showed significantly better efficacy than fluorides monotherapy for occlusal early caries lesions (mean difference: -21.02, 95% confidence interval: -27.94, -14.10, P<0.01). However, further well-designed studies are still needed.