We have reported that Erbin expression was down-regulated in the Jurkat leukaemia T lymphocytes treated with the recombinant soluble tumour necrosis factor-related apoptosis-inducing ligand (rsTRAIL). Herein, we studied the expression and the regulation of Erbin and its binding partner, ErbB2, in the MCF-7 breast cancer cell line. We showed that the expressions of Erbin and ErbB2 were modulated by PKCδ inhibitor, rottlerin, in the TRAIL-resistant MCF-7 cell line. The affinity of Erbin–ErbB2 interaction was reduced by ErbB2 phosphorylation. Inhibiting the expression of Erbin facilitated the sensitivity of the MCF-7 cells to TRAIL via suppressing the ErbB2/AKT/NF-κB signalling pathway.