This study aimed to examine the effect of the interaction between seaweed (laver, kelp, and sea mustard) intake and lipoprotein lipase gene (LPL) rs17482735 genotypes on the incidence of metabolic syndrome (MetS). The Korean Genome and Epidemiology Study (KoGES) data of Korean adults aged 40–69 years were used in this study. Information on seaweed intake was obtained from the food frequency questionnaire. To investigate the interaction between seaweed intake andLPLrs17482735 genotypes on the incidence of MetS, multivariable Cox proportional hazard models were used after adjusting for confounding variables. There was no significant association in women, but men with TG and TT genotypes of rs17482753 had lower incidence of MetS (HR 0.83, 95% CI 0.71–0.95,p-value = 0.01), low HDL-cholesterol levels (HR 0.81, 95% CI 0.69–0.95,p-value = 0.01), high triglyceride levels (HR 0.83, 95% CI 0.70–0.99,p-value = 0.0471), and high blood pressure (HR 0.79, 95% CI 0.67–0.93,p-value = 0.004). Furthermore, the incidence of MetS was lower in men with the highest laver and total seaweed intake and TG and TT genotypes of rs17482735 (HR 0.60, 95% CI 0.43–0.84; HR 0.57, 95% CI 0.41–0.79, respectively). High seaweed intake was negatively associated with MetS, suggesting thatLPLgenetic variations, particularly in men, may be helpful in preventing MetS. These results demonstrate that seaweed intake consideringLPLgenotypes may be beneficial for preventing and treating MetS.