The mechanisms of hypertrophic cardiomyopathy (HCM) pathogenesis can be investigated by determining the differences between healthy and disease states at the molecular level. In the present study, large-scale transcriptome sequencing was performed to compare mRNA expression in patients with HCM and control groups using an Illumina sequencing platform. Compared with the genome background, 257 differentially expressed genes (DEGs) were identified in which 62 genes were downregulated and 195 genes were upregulated. Reverse transcription-quantitative polymerase chain reaction was performed to validate the expression pattern of certain mRNAs. Gene ontology enrichment and KEGG analysis of mRNAs was conducted to identify the biological modules and pathological pathways associated with the DEGs. To the best of our knowledge, this is the first time study to investigate the differences in mRNA between patients with HCM and normal controls at the transcriptome level. The results of the study will contributed to the understanding of the important molecular mechanisms involved in HCM and aid the selection of key genes to investigate in the future.