Background: Basic studies have found that xanthine oxidase inhibitors extracted from mushrooms have inhibitory effects on hyperuricemia. However, the association between mushroom consumption and hyperuricemia is unknown in humans. Objective: We therefore designed a large-scale cohort study to examine whether mushroom consumption is a protective factor for developing hyperuricemia in adults. Methods: This prospective cohort study investigated 19 830 participants (mean age: 39.4 years; and 9906 [50.0%] men) who were free of hyperuricemia, cardiovascular disease, and cancer at the baseline. Mushroom consumption was measured at the baseline using a validated food frequency questionnaire. Hyperuricemia is defined as serum uric acid levels >420 μmol L-1 in men and >350 μmol L-1 in women. Cox proportional hazards regression models were used to examine the association of mushroom consumption with incident hyperuricemia. Restricted cubic spline regression was used to estimate the dose-response relationship between mushroom consumption and risk of hyperuricemia. Results: A total of 4260 first incident cases of hyperuricemia occurred during 61 421 person-years of follow-up (median follow-up of 4.2 years). After adjusting for demographic characteristics, lifestyle factors, dietary intake, and inflammatory markers, the multivariable hazard ratios (95% confidence intervals) for incident hyperuricemia were 1.00(reference) for <1.76 g per 1000 kcal per day, 0.93(0.86, 1.01) for 1.76-2.84 g per 1000 kcal per day, 0.93(0.85, 1.01) for 2.85-5.52 g per 1000 kcal per day, and 0.88 (0.80, 0.96) for >5.52 g per 1000 kcal per day, respectively (P for trend = 0.007). Conclusions: This population-based prospective cohort study has firstly demonstrated that higher mushroom consumption is significantly associated with lower incidence of hyperuricemia among general adults.