We showed that optimised immunoconjugates expressing high FHR4 valences were the most potent immunoconjugates to activate AP and subsequently induce massive C3b deposition, MAC binding and CDC of SK‐OV‐3, BT474 and SK‐BR3 HER2‐overexpressing tumour cell lines, as well as complement‐mediated phagocytosis. Here, CFHR4 is linked to neoplasm.