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Abstract Background Low health literacy often has an association with poor health outcomes such as low levels of self-efficacy, increased mortality, poor health status and reduced quality of life (QOL). The aim of the study was to quantitatively evaluate the relationship between health literacy (HL) and QOL based on a systematic review and meta-analysis. Methods EMBASE, PubMed, Web of Science, Elsevier, Cochrane Library, and Chinese electronic databases such as CNKI, and Wanfang were searched from 1970 until February 1, 2018. The pooled correlation coefficient (PCOR) and its 95% confidence interval (CI) between HL and QOL were estimated using R software. Potential sources of heterogeneity were explored using subgroup analysis, sensitivity analysis, and meta-regression. Results Twenty-three studies, with a total of 12,303 subjects,were included. The PCOR between HL and QOL was 0.35 (95%CI: 0.25–0.44). Considering different dimensions of HL, the PCOR between QOL and health knowledge, health behavior, health belief, and health skill were 0.36 (95% CI: 0.04–0.61), 0.36 (95%CI: 0.13–0.55), 0.39 (95%CI: 0.10–0.62), and 0.42 (95%CI: 0.03–0.69), respectively. The PCOR between HL and the two dimensions of QOL was lower than the total PCOR between HL and QOL. In subgroup analysis, the PCOR between HL and QOL was 0.46 (95%CI: 0.13, 0.69) among community residents, 0.45 (95%CI: 0.27, 0.61) in China, and 0.45 (95%CI: 0.24, 0.62) based on cohort studies. Sensitivity analyses showed that the stability of results had no significant after excluding the study (p