Hyperuricemia in children is associated with increased risk of high blood pressure, metabolic syndrome, and future cardiovascular disease. Serum perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) levels have been shown to be positively associated with hyperuricemia in adults, but the association in children remains unexplored. We therefore examined the association between serum PFOA and PFOS levels and hyperuricemia in a representative sample of US children. A cross-sectional study was performed on 1,772 participants ≤18 years of age from the National Health and Nutrition Examination Survey 1999–2000 and 2003–2008. The main outcome of interest was hyperuricemia, defined as serum uric acid levels ≥6 mg/dL. We found that serum levels of PFOA and PFOS were positively associated with hyperuricemia, independent of age, sex, race/ethnicity, body mass index, annual household income, physical activity, serum total cholesterol, and serum cotinine levels. Compared with subjects in quartile 1 (referent), subjects in quartile 4 had multivariable-adjusted odds ratios for hyperuricemia of 1.62 (95% confidence interval: 1.10, 2.37) for PFOA and 1.65 (95% confidence interval: 1.10, 2.49) for PFOS. Our findings indicate that serum perfluoroalkyl chemical levels are significantly associated with hyperuricemia in children even at the lower “background” exposure levels of the US general population.