Cancer patients frequently suffer from anemia and cancer-related pain, which can be treated by non-opioid analgesics like Diclofenac (DCF) and Acetaminophen (APAP) attenuating inflammatory responses. The key pro-inflammatory cytokine interleukin (IL)-6 triggers expression of acute phase proteins, including the iron regulator hepcidin. We show by quantitative proteomics and dynamic pathway modelling that DCF and APAP enhance the induction of the feedback-inhibitor SOCS3 and reduce IL-6 mediated STAT3 phosphorylation in hepatoma cells. Consequently, expression of acute phase proteins is decreased with the exception of hepcidin. Our mathematical modelling approach reveals that due to an autocrine activation loop of BMP signaling hepcidin expression in hepatoma cells is amplified and this loop is absent in primary hepatocytes. We experimentally validate our model-based prediction that co-inhibition of the BMP receptor is most promising to reduce excessive hepcidin production in hepatoma cells and could be exploited to prevent iron deficiency caused anemia in liver cancer.