Hyperuricemia has received increasing attention as a major public health problem. This study aims to investigate the risk factors for hyperuricemia and to explore the relationship between changes in biochemical variables and incident hyperuricemia.A cross-sectional and subsequently prospective study was performed among adults who took their health checkups at Zhejiang University Hospital. The participants who were free of hyperuricemia at baseline received annual follow-up examinations during a 6-year period. Cox proportional hazards regression analyses were conducted to calculate the risks for incident hyperuricemia.Of the 9238 participants enrolled, 1704 (18.4%) were diagnosed as hyperuricemia. During 21,757 person-years of follow-up, 1492 incident hyperuricemia cases were identified. The incidence of hyperuricemia was 68.58 cases per 1000 person-year of follow-up in the overall participants. The prevalence and the incidence of hyperuricemia increased greatly in female older than 50 years. High levels of BMI, SBP, FPG, TG, LDL-C, ALT, BUN, and creatinine increased the risk of hyperuricemia. Suffering fatty liver also increased the risk of hyperuricemia. Subjects with increasing DBP, TG, BUN, creatinine, or decreasing HDL-C were more likely to incident hyperuricemia.This study revealed that the change of diastolic blood pressure (DBP), serum triglycerides (TG), blood urea nitrogen (BUN), creatinine, and high-density lipoprotein cholesterol (HDL-C) level were independently associated with incident hyperuricemia.