Long-term use of nucleoside ( nucleotide ) analogues for anti-HBV treatment care easily lead to drug resistance. As compared to genotypic resistance detection, the detection technology of phenotypic resistance is a method used to analysis the sensitivity of antiviral drugs in vitro cell model, the result can directly reflect the relationship between drug-resistance mutations and drug susceptibility, thus perform a better prediction of clinical resistance.Among those technologies, some analysis strategies like transient transfection assay, stable cell lines and enzymatic assay, have been developed for early diagnoses as well as dynamic monitoring of drug resistance, and contribute greatly to proper selection of therapeutic regimen, reduction of resistance rate and implementation of individual treatment.