When conveying information about routes to follow in complex environments, human route-givers adapt to route-receivers’ familiarity with the environments in their choice of landmarks. Meanwhile, as route-givers themselves have experienced the environments within a social role, the landmarks they select may also differ significantly. This research investigated how these two factors influence landmark selection when communicating routes in indoor environments. Two groups of participants were recruited to conduct indoor landmark selection experiments for familiar and unfamiliar route-receivers in a multi-functional university building. The results show an interaction effect between these factors in indoor landmark selection. These findings lay an empirical ground for developing human-centered mobile navigation systems that can adapt to users’ social roles and their familiarity with the environment.