The impact of interleukin-10 (IL-10) gene promoter polymorphisms (SNPs) on treatment response in HCV patients was dissimilarly estimated. Hence, the aim of this meta-analysis was to robustly assess the effect of IL-10 SNPs on treatment response in HCV patients. An electronic literature search was carried out through PubMed, EMBASE, Web of science, and Scopus databases. Studies assessing the association between IL-10 polymorphisms and treatment response in HCV patients were included. Studies were excluded if genotype frequencies are not consistent with the Hardy-Weinberg Equilibrium (HWE) or in case of including patients with hepatitis B virus coinfection. Risk of bias in included studies was assessed using the Newcastle-Ottawa Scale. Meta-analyses were performed for the influence of IL-10 gene promoter SNPs (rs1800896 (-1082 A/G), rs1800871 (-819 C/T), and rs1800872 (-592 C/T)) and haplotypes on treatment response in HCV patients. Subgroup analyses, meta-regressions, publication bias assessment, and sensitivity analyses were also conducted. Overall, 32 studies with a total of 5943 HCV cases and 2697 controls were included in the present study. The -1082*G allele was significantly associated with increased risk of non-response (NR) to treatment, OR 95% CI = 1.29 1.1-1.51, = .002. Besides, the rs1800872 -592*C allele was significantly associated with increased NR risk, OR 95% CI = 1.22 1.02-1.46, = .03. Subgroup analysis showed that this association remained significant only in patients treated with PEG-IFN alone, = .01. The -1082*G/-819*C/-592*C (GCC) haplotype was significantly associated with increased NR risk, OR 95% CI = 1.62 1.13-2.23, = .009. Our results suggest that the IL-10 rs1800896 was associated with NR risk especially in North-African and Asian populations. Moreover, the IL-10 gene promoter -1082*G/-819*C/-592*C (GCC) haplotype which has been associated with higher production of IL-10, was significantly associated with increased NR risk.