Background: Casein Kinase 2 (CK2) is a ubiquitous cellular serine-threonine kinase with broad spectrum of substrates. This enzyme is widely expressed in eukaryotic cells and is overexpressed in different human cancers. Thus, the inhibition of CK2 can induce the physiological process of apoptosis leading to tumor cell death. Objective: Selecting natural inhibitors toward the target enzyme using database mining. Method: With our continuous effort to discover new compounds with CK2 inhibitory effect, several commercial natural databases were searched using molecular modeling approach and the selected compounds were evaluated in vitro. Result: Three compounds were selected as candidates and evaluated in vitro using CK2 holoenzyme, their effect on three cancer cell lines was determined. The selected candidates were weak inhibitors toward the target enzyme, only one compound showed moderate effect on cell viability. Conclusion: Several natural databases were screened and compounds were selected and tested in vitro, despite of the unexpected low activity of the compounds, this study can help in directing the search of potent CK2 inhibitors and better understand the binding requirements of the ATP competitive inhibitors.