We aimed to investigate the cross-sectional associations of serum fatty acid (FA) and related Δ-desaturase with hypertension among 2,447 community-dwellers aged 35-79 years living in Zhejiang Province, China. Individual FA was determined in serum, Δ(5)-desaturase (D5D) and Δ(6)-desaturase (D6D) activities were indirectly estimated by FA product/precursor ratios. Participants in the highest quartile of D5D component scores (20:4n-6, 20:5n-3, 22:6n-3 and D5D) have significantly lower odds of hypertension compared with individuals in the lowest (multivariate-adjusted odds ratio (OR) = 0.68, 95% CI: 0.46-0.98). When further stratified by gender, high D5D component scores were significantly associated with lower odds of hypertension in women (OR = 0.53, 95% CI: 0.35-0.80), but not in men (OR = 0.78, 95% CI: 0.52-1.18). Multivariate-adjusted prevalent OR for an interquartile increment of individual FA and estimated desaturase was 1.27 (95% CI: 1.08-1.50) for 16:0, 1.15 (95% CI: 1.01-1.30) for 16:1n-7, 0.89 (95% CI: 0.80-0.99) for 22:6n-3, 1.32 (95% CI: 1.01-1.72) for D6D (18:3n-6/18:2n-6), and 0.74 (95% CI: 0.56, 0.98) for D5D (20:4n-6/20:3n-6). Present findings suggested that high serum 22:6n-3 and D5D as well as low 16:0, 16:1n-7 and D6D were associated with a low prevalence of hypertension in this Chinese population.