Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays an important role in coronary heart disease (CHD). This study was aimed to investigate the associations of polymorphisms (R92H, V279F, I198T, and A379V) in PLA2G7 with CHD. A total of 322 patients with CHD and 414 CHD-free controls were included in the study. Polymorphisms in PLA2G7 were sequenced by DNA Sequencer and statistical analyses were performed to study the associations between polymorphisms and CHD. RH + HH genotype, RH genotype, and H allele of R92H were significantly associated with an increased risk of CHD (P = 0.005, P = 0.009, and P = 0.003, respectively), while no associations were observed between V279F and I198T and CHD (A379V was not analyzed because of deviation from Hardy–Weinberg equilibrium). Correlations between R92H and CHD still existed after adjustment for confounding risk factors of CHD (P = 0.001). Furthermore, stratified analyses showed subgroups of the senior, hypertension, non-smoking, non-diabetics, and male subjects brought a higher risk for CHD (P = 0.015, P = 0.001, P = 0.001, P = 0.002, and P = 0.004, respectively). We also observed a lower level of protective factor HDL-C in CHD patients carrying genotype RH + HH than patients with RR (P = 0.047). Furthermore, we conducted haplotype analysis and detected more harmful effects of haplotypes HVI and RVT as compared with other haplotypes (P = 2.538 × 10−3 and P = 0.031). These findings indicated that R92H variant in PLA2G7 gene might contribute to CHD susceptibility in a southern Chinese population.