Aim To summarize the gene mutation analysis and clinical treatment of a Chinese familial hypercholesterolemia family. Methods The proband was admitted to hospital due to “repeated asthma with chest pain for 4 months, aggravated for 2 days”, abnormally elevated plasma low density lipoprotein cholesterol (LDLC) and early onset of coronary heart disease. Whole exon sequencing was performed in the proband, and apolipoprotein E (ApoE), paraoxonase1(PON1), proprotein convertase subtilisin/kexin type 9 (PCSK9) and other sites were sequentially analyzed, and suspected pathogenic mutations were detected in family members. Coronary intervention and lipid-lowering therapy were performed in the proband and his father. Results The proband, his father and his son all had six mutations in the LDLR gene including c.191+13G＞A(rs200621482), c.1598G＞T(rs200427089), c.883T＞G(rs553235458), c.3536A＞G(rs201300867), c.2215+6G＞A(rs540060615), c.162+5A＞T(rs146596406), respectively. Heterozygous mutations were found in all 6 loci of the three patients. The ApoE genotypes of the three patients were as follows:ApoE genotypes of both the proband and his son were ε3/ε3, and the protein phenotype was E3 (CC at ApoE2 and TT at ApoE4); ApoE genotypes of his father was ε2/ε3, and the protein phenotype was E2(CT at ApoE2 and TT at ApoE4). The PON1(A575G, rs662) locus genotypes of three patients were AG, and the PCSK9 genotypes of three patients were GG, CC, CC and GG.Based on the results of the family genetic test, the proband and his father were given an individualized lipid-lowering regimen, atorvastatin calcium combined with ezetimibe and PCSK9 inhibitors, and the proband and his father were successfully treated with coronary interventionary therapy, and LDLC was normal with no adverse drug reactions during follow-up of two years. Conclusion In this study, 6 mutations of LDLR gene were found in all patients of this family, among which LDLR c.191+13G＞A and c.162+5A＞T were not reported in China, which enriched the mutation spectrum of LDLR gene in Chinese population. This study is helpful to elucidate the pathogenesis of FH and further guide the clinical treatment of FH patients.