The aim of the present study was to evaluate the association between hyperuricemia and osteoporosis in a Korean population. Data from participants of the Korean Genome and Epidemiology Study who were ≥ 40 years old were collected from 2004 to 2016. Among 173,209 participants, 11,781 with hyperuricemia (> 7.0 mg/dL in men and > 6.0 mg/dL in women) and 156,580 controls were selected based on serum measurements. Odds ratios (ORs) of osteoporosis between individuals with hyperuricemia and controls were analyzed using a logistic regression model. In the adjusted model, age, sex, income group, body mass index, smoking, alcohol consumption, hypertension, diabetes mellitus, hyperlipidemia history and nutritional intake were adjusted. The adjusted OR (aOR) of osteoporosis was 0.79 [95% confidence interval (CI) = 0.71-0.87, P < 0.001]. In subgroup analyses according to age and sex, statistical significance was observed in men > 60 years old and in women > 50 years old. In another subgroup analysis according to past medical history, significant differences were found according to hypertension (aOR = 0.83, 95% CI = 0.73-0.94, and 0.75, 95% CI = 0.64-0.87), diabetes mellitus (aOR = 0.77, 95% CI = 0.69-0.86), and hyperlipidemia (aOR = 0.74, 95% CI = 0.61-0.89, and 0.81, 95% CI = 0.72-0.91). This study demonstrated that hyperuricemia was associated with a decreased risk of osteoporosis.