Anthropomorphic roles are widely used in marketing communication, but previous studies have focused on the effects of various anthropomorphic characteristics on advertising effectiveness, and few studies have examined how the consumer’s need for uniqueness affect the communication effects of virtual anthropomorphic spokespersons. Through three experiments, this article examines the interaction effect between two types of spokespersons (human vs. virtual spokespersons) and the level of the consumer’s need for uniqueness (low to high) on persuasiveness. Study 1 shows that the persuasive effect of different types of spokespersons is moderated by the level of consumer’s need for uniqueness, among which: consumers with high need for uniqueness respond more positively to virtual spokespersons. Study 2 further finds that the interaction effect between the need for uniqueness and the type of spokesperson is mediated by positive emotions. Study 3 adds brand types (luxury brand vs. mass brand) for a three-way interaction effect test, and the results show that: in the mass brand advertisements, virtual spokespersons are more persuasive to consumers with high need for uniqueness than human spokespersons. However, this moderating effect is not significantly different in luxury brand advertising.