Objective: This case-control study explored correlations between LP-PLA2 gene polymorphisms (A379V, V279F, and R92H) and susceptibility and severity of acute pancreatitis (AP) in a Chinese population. Materials and Methods: From October 2013 to October 2015, 94 AP patients were chosen as the case group. According to the Acute Physiology and Chronic Health Evaluation (APACHE) II score standard, AP patients were divided into a mild AP (MAP) group (n = 46) and severe AP (SAP) group (n = 48). The 48 SAP patients were further divided into an SAP with multiple organ dysfunction syndrome (MODS) group (n = 42) and SAP without MODS group (n = 6). Meanwhile, 96 healthy subjects who received physical examinations at the study hospitals were selected as the control group. Serum lipoprotein-associated phospholipase A2 (LP-PLA2) levels were detected by an enzyme-linked immunosorbent assay (ELISA). The A379V (s1051931), V279F (rs16874954), and R92H (rs13989) polymorphisms of the LP-PLA2 gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There were significant differences in the frequencies of the LP-PLA2 gene polymorphisms between the AP group and the control group. The distribution of V279F-AA+AC genotype and R92H-AA+AG genotype in the AP group was higher than that in the control group, whereas the SAP group and SAP with MODS group distributions were higher than those in the MAP group and SAP without MODS group (both p < 0.05). G-C-A, G-A-G, and G-C-G haploids formed by A379V, V279F, and R92H may be associated with AP susceptibility. LP-PLA2 gene polymorphisms could affect serum LP-PLA2 level, whereas the V279F-A allele gene, the R92H-A allele gene, serum LP-PLA2 level, and serum amylase may be independent risk factors for AP (all p < 0.05). Conclusion: These results demonstrated that the LP-PLA2 gene polymorphisms, V279F and R92H, may be associated with susceptibility to and severity of AP.