The lymphotoxin-β receptor (LTβR) gene is involved in autoimmune disease and inflammatory disorder development, but the relationship between LTβR and benign prostatic hyperplasia (BPH) is unclear. In total, 222 with BPH were examined for 3 single nucleotide polymorphisms [rs3759333 (-1387C/T), rs3759334 (-1326A/G), and rs2364480 (Ala172Ala)] located in the promoter and coding regions of LTβR using direct sequencing. The genotype distributions of rs3759334 were associated with prostate volume larger than 40 g. There were significant differences between the small (<40 g) and large (≥40 g) group subjects [codominant 1 model: odds ratio (OR) = 4.65, 95% confidence interval (CI) = 1.95-11.09, P = 0.001; dominant model: OR = 4.91, 95%CI = 2.07-11.63, P = 0.0002; log-additive model: OR = 4.81, 95%CI = 2.05-11.24, P = 0.0001]. The allele distributions of rs3759334 were significantly associated with BPH (OR = 4.87, 95%CI = 2.16-10.99, P = 0.0001). The distribution of rs2364480 was significantly different between groups (codominant 1 model: OR = 2.17, 95%CI = 1.11-4.26, P = 0.028; dominant model: OR = 2.16, 95%CI = 1.13-4.12, P = 0.019; log-additive model: OR = 1.86, 95%CI = 1.07-3.24, P = 0.027). The allele distribution of rs2364480 was significantly associated with BPH (OR = 1.88, 95%CI = 1.08-3.30, P = 0.027). We found that LTβR polymorphisms caused severe BPH. Thus, LTβR may contribute to the risk of BPH development.