Virtual reality (VR) is increasingly used in the study and treatment of paranoia. This is based on the finding that people who mistakenly perceive hostile intent from other people also perceive similar threat from virtual characters. However, there has been no study of the programming characteristics of virtual characters that may influence their interpretation. We set out to investigate how the animation and expressions of virtual humans may affect paranoia. In a two-by-two factor, between-groups, randomized design, 122 individuals with elevated paranoia rated their perceptions of virtual humans, set in an eye-tracking enabled VR lift scenario, that varied in facial animation (static or animated) and expression (neutral or positive). Both facial animation (group difference = 102.328 [51.783, 152.872], p < 0.001, $${\eta }_{p}^{2}\hspace{0.17em}$$
η
p
2
= 0.125) and positive expressions (group difference = 53.016 [0.054, 105.979], p = 0.049, $${\eta }_{p}^{2}\hspace{0.17em}$$
η
p
2
= 0.033) led to less triggering of paranoid thoughts about the virtual humans. Facial animation (group difference = 2.442 [− 4.161, − 0.724], p = 0.006, $${\eta }_{p}^{2}\hspace{0.17em}$$
η
p
2
= 0.063) but not positive expressions (group difference = 0.344 [− 1.429, 2.110], p = 0.681, $${\eta }_{p}^{2}\hspace{0.17em}$$
η
p
2
= 0.001) significantly increased the likelihood of neutral thoughts about the characters. Our study shows that the detailed programming of virtual humans can impact the occurrence of paranoid thoughts in VR. The programming of virtual humans needs careful consideration depending on the purpose of their use.