The human coronavirus OC43 is a major contributor to the common cold worldwide, though due to its low mortality rate, little research has focused on this human pathogen. The nucleocapsid is an essential structural protein with conserved functions across the coronavirus family. While a multitude of studies have examined nucleocapsid function, none have described the effects of OC43 nucleocapsid on the transcription factor NF-kappaB. We report that the nucleocapsid protein of OC43 causes potentiation of NF-kappaB activation. This prolonged activation is the direct result of the ability of the nucleocapsid to bind RNA, specifically microRNA 9 (miR-9), which is a negative regulator of NF-kappaB. This previously undescribed interaction between virus and host is a potential mechanism of immune evasion in RNA viruses.