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Our previous study identified that the RepA protein encoded by the oat dwarf virus (ODV) was responsible for inducing a strong hypersensitive response (HR) during the virus infection in non-host tobacco plants. However, little was known about the molecular mechanism of the RepA-elicited HR. Here, a RING-finger protein, which is described as NbRFP1 and is mainly located in the cytoplasm and nucleus in <i>Nicotiana benthamiana</i> cells, was confirmed to interact with RepA. In addition, the accumulation level of <i>NbRFP1</i> in <i>N. benthamiana</i> leaves was enhanced by either ODV infection or by only RepA expression. The knockdown of <i>NbRFP1</i> by a TRV-mediated virus-induced gene silencing markedly delayed the ODV or RepA-elicited HR. By contrast, the overexpression of <i>NbRFP1</i> in <i>N. benthamiana</i> conferred enhanced resistance to ODV infection and promoted RepA-induced HR. Further mutation analysis showed that a RING-finger domain located in NbRFP1 plays important roles in modulating RepA-induced HR, as well as in mediating the interaction between NbRFP1 and RepA.