TRANSPARENT TESTA GLABRA (TTG) proteins that contain the WD40 protein interaction domain are implicated in multiple signalling pathways in plants. The salicylic acid (SA) signalling pathway regulates the resistance of plants to pathogens through defence responses via pathogenesis-related (PR) gene transcription activated by the NPR1 (nonexpresser of PR genes 1) protein, which contains WD40-binding domains. In this study, we report that tobacco (Nicotiana tabacum) NtTTG2 quells the resistance to viral and bacterial pathogens by repressing the nuclear localisation of NPR1 and SA/NPR1-regulated defence in plants. Nullification of the NtTTG2 protein production by silencing of the NtTTG2 gene resulted in the enhancement of resistance and PR gene expression, but NtTTG2 overexpression or NtTTG2 protein overproduction caused the opposite effects. Concurrent NtTTG2 and NPR1 gene silencing or NtTTG2 silencing in the absence of SA accumulation compensated for the compromised defence as a result of the NPR1 single-gene silencing or due to the absence of SA. To our surprise, NtTTG2 did not interact with NPR1 but was able to modulate the subcellular localisation of the NPR1 protein. When the production of NtTTG2 was nullified, NPR1 was found predominantly in the nucleus and the PR genes were expressed. On the contrary, when NtTTG2 accumulated in transgenic plants, a large proportion of NPR1 was retained in the cytoplasm and the PR genes were not expressed. These results suggest that NtTTG2 represses SA/NPR1-regulated defence by sequestering NPR1 from nuclear localisation and the transcriptional activation of the defence-response genes.