Chemokine genes may influence both hepatitis C virus (HCV) spontaneous clearance in acute infection and treatment response in chronic infection. We conducted this study to evaluate whether the genetic variants in several CC family genes influence HCV spontaneous clearance and treatment response. The current research genotyped eight SNPs, including CCR1 rs3733096, rs13096371, CCR5 rs746492, rs1800874, CCL3 rs1130371, CCL5 rs3817656, CCL8 rs1133763, CCL14 rs854625, to explore their associations with HCV spontaneous clearance and response to treatment in two populations. We identified that the CCR1 rs3733096 (dominant model: adjusted OR = 2.29, 95% CI = 1.49-3.53, additive model: adjusted OR = 2.21, 95% CI = 1.50-3.25) and CCL5 rs3817656 (dominant model: OR = 1.37, 95% CI = 1.10-1.70, additive model: OR = 1.33, 95% CI = 1.12-1.58) were associated with HCV spontaneous clearance in Chinese Han population, while we found no association with treatment response. Moreover, the expression quantitative trait loci (eQTL) analysis showed that the risk alleles of rs3817656 were significantly associated with downregulated expression of CCL5 in whole blood (P < 0.001). The polymorphism of CCR1 rs3733096 and CCL5 rs3817656 are associated with spontaneous clearance of HCV in Chinese Han population.