Abstract The use of hepatocyte cell lines as a replacement for animal models have been heavily criticised mainly due to low expression of metabolism enzymes. This study compares primary human hepatocytes with the C3A cell line and with respect to their response to a panel of nanomaterials (NMs; two ZnO, two MWCNTs, one Ag and one positively functionalised TiO(2)). The cell line was very comparable with the primary hepatocytes with regards to their cytotoxic response to the NMs (Ag > uncoated ZnO > coated ZnO). The LC(50) was not attained in the presence of the MWCNTs and the TiO(2) NMs. All NMs significantly increased IL-8 production, with no change in levels of TNF-a and IL-6. Albumin production was measured as an indicator of hepatic function. The authors found no change in levels of albumin with the exception of the coated ZnO NM at the LC(50) concentration. NM uptake was similar for both the primary hepatocytes and C3A cells as investigated by TEM. Meanwhile, the authors confirmed greater levels of CYP450 activity in untreated primary cells. This study demonstrates that the C3A cell line is a good model for investigating NM-induced hepatocyte responses with respect to uptake, cytotoxicity, pro-inflammatory cytokine production and albumin production.