Chinese medicine formula (CMF) usually contains multiple herbs and its components are very complicated, which therapeutic effects are derived from the integrative activity of multiple components. Therefore, the screening of bioactive compounds in the formula is necessary, though it is very difficult, not only for elucidating the therapeutic components but also for developing the quality control method. In this work, three cell lines fishing combined with LC-MS analysis was developed for screening the potential bioactive compounds in Fuzhengzhiyanghefuzhiyang decoction (FZHFZY), a CMF for the treatment of psoriasis in clinic. Nineteen potential active compounds were discovered and thirteen of them were identified as rehmannioside D, melittoside or rehmannioside A, tufulingoside, neoastilbin, astilbin, neoisoastilbin, isoastilbin, engeletin, isoengeletin, spinosin, cnidimoside A, rutaevin and limonin, respectively. The effects of identified components were also analyzed in vitro. The results showed that IL-1β expression of RAW 264.7 cells treated with spinosin and melittoside as well as the TNF-α level of RAW 264.7 cells treated with rehmannioside D and melittoside were not significantly different compared with lipopolysaccharide (LPS)-treated cells. Though all identified potential active components had no apoptosis effect to HaCaT cells, rehmannioside D, rehmannioside A, astilbin and neoisoastilbin could significantly suppress HUVEC cells migration compared with control. These results indicated that the target cell fishing combined with LC-MS analysis is a useful tool for screening bioactive compounds from complicated CMF, and the identified active components may mainly contribute to the therapeutic effects of FZHFZY.