Hepatitis B virus genotype sequence variations constitute the primary determinant of DNA quantitative detection accuracy. The established correlation between genotype characteristics and detection targets reveals that genetic sequence variations, replication activity differences, and specific mutations create interference mechanisms across target recognition, amplification efficiency, and signal capture processes. This study proposes integrated strategies including detection technology optimization, multi-genotype calibration, and standardized clinical interpretation protocols. By implementing targeted optimized detection systems and standardized application protocols to mitigate genotype interference, this approach enhances detection accuracy and clinical applicability, thereby providing reliable experimental evidence for precision diagnosis and treatment of hepatitis B.