<b><i>Background:</i></b> It has been reported that interferon-λ3 (<i>IFNL3)</i>might influence the pathogenesis and clearance of human papillomavirus (HPV) infection. The impact of <i>IFNL3</i> single-nucleotide polymorphism (SNP) on HPV infection is currently unknown. The aim of this study was to investigate the association between variants in the <i>IFNL3</i> region and HPV infection in women with human immunodeficiency virus (HIV) infection. <b><i>Methods:</i></b> A total of 236 HIV patients, including 65 HPV-negative and 171 HPV DNA-positive women, were enrolled into this study. The <i>IFNL3</i> rs12979860 polymorphism was genotyped using a predesigned TaqMan SNP genotyping assay. <b><i>Results:</i></b> Data showed no significant differences in genotypes or allele frequencies between the HPV DNA-positive and the HPV-negative women (<i>p</i> > 0.05). After dividing the HPV-positive women according to cytology results into patients with abnormal and normal lesions, the genotype and allele distribution of the SNP did not significantly differ between the 2 groups (<i>p</i> > 0.05). <b><i>Conclusions:</i></b> Our results showed that the <i>IFNL3</i> rs12979860 polymorphism is not a major determinant of the susceptibility to HPV infection and their progression to abnormal cervical lesions in women living with HIV.