Aims: Hypertrophic cardiomyopathy (HCM) mainly results from autosomal-dominant inherited single heterozygous mutations in cardiac sarcomere genes. Arrhythmia such as ventricular tachycardia and fibrillation is one of the main causes of sudden death especially in young HCM patients. Genetic background contributions to arrhythmogenesis in HCM patients were investigated. Methods: One hundred and thirteen HCM probands with both clinical diagnosis and positive gene screening results were investigated. Ninety-six 96 cardiac relative genes exon and boarding intron were analysis using second-generation sequencing. The identified mutations were confirmed by bi-directional Sanger sequencing and 300 healthy controls. Results: The results showed the incidence of male was higher than female (1.69:1). Ten patients were less than 19 years old, 8.08%. The 40-49 years old group took 35.4%. Twenty five patients (22.1%) carried single mutation, 88 patients (77.9%) carried two or more mutations. In 96 gene tested, mutations were identified in 69 genes. The detection rate was >5% in 9 genes, including TTN (61.95%)，MYH7 (24.78%)，OBSCN (23.89%)，MYBPC3 (23.01%)，ANK2 (8.85%)，RYR2 (7.08%)，SCN5A (7.08%)，AKAP9 (5.31%)，DMD (5.31%)，and DSG2 (5.31%).Fifty nine (52.21%) patients were found carried cardiac arrhythmic relative gene mutations. Thus, 20 patients (17.70%) carried long QT syndrome related genes. Others included Brudaga syndrome 17 (15.04%), short QT syndrome 7 (6.19%), atrial fibrillation 5 (4.42%), sick sinus syndrome 10 (8.85%), catecholaminergic polymorphic ventricular tachycardias 9 (7.96%), and arrhythmogenic right ventricular cardiomyopathy 19 patients (16.81%) respectively. Then a three generation family with four missense mutations was intensively investigated. These were two novel MYH7-H1717Q and MYLK2-K324E mutations accompanied by the KCNQ1-R190W and TMEM70-I147T mutations. The proband carried all four mutations with dual HCM and LQT1 phenotypes. Five subjects carried two mutations. II-1 only carried TMEM70-I147T. Left ventricle mass indexes in MYH7-H1717Q carriers were significantly higher than in non-H1717Q carriers (90.05±7.33g/m2, 63.20±4.53 g/m2 respectively, P<0.01). Four KCNQ1-R190W carriers showed QTc intervals that were significantly more prolonged than those in non-R190W carriers (472.25±16.18 ms and 408.50±7.66 ms respectively, P<0.05). All MYLK2-K324E carriers showed inverted ECG T waves. The subject with only a TMEM70-I147T mutation showed normal ECG and echocardiographs suggesting that this had less pathological effects at least in this family. Conclusion: Multi gene mutations contribute HCM phenotypes. Arrhythmic associated gene mutation might be the genetic background for rrhythmogenesis in HCM patients.