Objective To explore the application value of digital PCR technology in detecting BRAF V600E and TERT C250T, C228T gene mutations in the diagnosis and prognosis assessment of thyroid nodules. Methods A total of 2, 213 clinical samples of thyroid nodules submitted to Zhengzhou KingMed Clinical Laboratory Center from January 2020 to December 2025 were selected as the research subjects. The samples that underwent both amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and digital PCR techniques for detecting BRAF V600E gene mutations were 418 cases and 1, 795 cases respectively, with sanger sequencing or next-generation sequencing (NGS) results serving as the gold standard. Among them, 1,795 patients also underwent digital PCR testing for TERT C250T and C228T gene mutations. The diagnostic efficacy of the two detection methods was analyzed, and the quantitative ability, sample applicability, and reportability of Digital PCR detection were evaluated. Additionally, the value of mutation abundance in prognosis assessment was preliminarily explored. Results Using the gold standard results as the reference, in 2, 213 samples of thyroid nodules, the sensitivity of ARMS-PCR for detecting BRAF V600E mutations was 70.82% (602/850), with a specificity of 100% (1,363/1,363); the sensitivity of digital PCR for detecting BRAF V600E mutations was 96.94% (824/850), with a specificity of 100% (1,363/1,363). The range of BRAF V600E mutation copy numbers detected by digital PCR was 5.40 -77 749.50, while the range of wild-type copy numbers was 177.80 181,386.50. The specimen types detected by digital PCR were not limited to wax block slides, but also included biopsy specimens. The DNA extraction concentration of the specimens was detected by QBIUT and ranged from 0.1 to 112 ng/μl; among them, 65 samples with DNA concentrations below the detection limit could be reported, and the sample reporting rate was 99.28%. Prognostic assessment showed that in the BRAF V600E high-abundance group (≥1.00%) detected by digital PCR, the incidence of TERT mutations and the risks of lymph node metastasis and extrathyroidal invasion were significantly higher than those in the lowabundance group, while ARMS-PCR could not provide such quantitative prognostic information. Conclusion Compared with the traditional ARMS-PCR method, digital PCR for detecting BRAF/TERT gene mutations has higher sensitivity. It has high value in detecting low-abundance mutations and handling low-quality samples. Moreover, its quantitative ability can provide important reference for the prognosis assessment of thyroid nodules.