Updated project metadata. To expand knowledge of the effects of interferon at the proteomic level, we treated HepG2 cells with IFN-alpha and IFN-lambda for 24 hours. HepG2.2.15 cells, a model for HBV infection, were also examined versus controls. MTT assays showed that optimized IFN levels (100 ng/ml) did not induce apoptosis relative to untreated controls. Including controls, more than 6,000 proteins were identified. Five replicates each of IFN-alpha treatment, IFN-lambda treatment, and control were performed, allowing confident identification of differentially expressed proteins. While a number of publications suggest that no interferon effect is evident upon HBV infection, our own results strongly suggest otherwise. Differential alterations of the proteasome were noted when comparing HBV infection against IFN-treatment. We also note that differential effects upon IFN treatment significantly overlapped with transcriptomic datasets when upregulation was examined. However, proteins downregulated upon IFN treatment show little overlap with these transcriptomic datasets.