In this study, Cabernet Sauvignon, the most cultivated wine grape cultivar in eastern Helan mountain of Ningxia was used as the test material. Based on the results in our previous experiments, the transcriptome sequences and the organic acids assay at different developmental stages of fruits, we further predicted the transcription factor binding sites with the functional gene promoter regions (target), combined with the differentially expressed gene analysis and the weighted gene coexpression network analysis (WGCNA), to select the transcription factors that specifically bind to the functional genes associated with malate biosynthesis in Cabernet Sauvignon fruits. In addition, qRTPCR was used to verify the regulation mechanism between these key functional genes and their transcription factors in different cultivation areas at different developmental stages. The results provide a theoretical basis and idea for genetic improvement of highquality wine grapes. The results show that: (1) GS/MS analysis found that fumarate and malate at the four developmental stages of Cabernet Sauvignon fruits had the same variation trend. Both of them gradually increased to the highest (3.63 and 626.53 μg/g) from the hard to green, then decreased slowly, and gradually decreased to the lowest level (2.14 and 244.26 μg/g) through the veraison to maturity. While the variation of oxaloacetate was opposite, the content is the highest (315.54 μg/g) at the hard, it drops to the lowest (126.11 μg/g) from the green, veraison to maturity gradually. (2) Transcriptome sequencing of Cabernet Sauvignon fruits developmental stages results showed a total of 6 411 transcription factors that may be combined with 12 functional genes of the malate biosynthetic pathway, among them there are 86 transcription factors associated with 3 functional genes of fumarate hydratase (FH), 717 transcription factors related to 10 functional genes of malate dehydrogenase (MDH). (3) Veen analysis of transcriptome sequencing data and the WGCNA analysis of organic acid contents determined 3 genes related to FH (VIT_14s0060g01700, VIT_13s0019g03330, VIT_07s0005g00880), 2 genes related to MDH (VIT_10s0003g01000, VIT_13s0019g05250) and 18 key transcription factors highly associated with malic acid biosynthesis during the ripening process in Cabernet Sauvignon fruits. (4) qRTPCR verification and correlation analysis showed that the expression levels of transcription factors VIT_01s0011g06200, VIT_08s0056g01230 of VIT_13s0019g03330, and transcription factors VIT_06s0004g04960, VIT_10s0003g02070 of VIT_13s0019g05250 are positively related to the malate accumulation, also suggested these 4 transcription factors may regulate the transcription of functional genes to influence the biosynthesis of malate comprehensively in Cabernet Sauvignon fruits.