Plant hormone salicylic acid (SA) plays critical roles in defense signaling against biotrophic pathogens. Pathogen inoculation leads to SA accumulation in plants. SA activates a transactivator protein NPR1, which, in turn, transcriptionally activates many defense response genes. Reports also suggest the presence of NPR1-independent pathways for SA signaling in Arabidopsis. Here, we report the characterization of a zinc-finger protein-coding gene AtOZF1 that positively influences NPR1-independent SA signaling. Mutants of AtOZF1 are compromised, whereas AtOZF1-overexpressing plants are hyperactive for defense against virulent and avirulent pathogens. AtOZF1 expression is SA-inducible. AtOZF1 function is not required for pathogenesis-associated biosynthesis and accumulation of SA. However, it is required for SA responsiveness. By generating atozf1npr1 double mutant, we show that contributions of these two genes are additive in terms of defense. We identified AtOZF1-interacting proteins by a yeast-two-hybrid screening of an Arabidopsis cDNA library. VDAC2 and NHL3 are two AtOZF1-interacting proteins, which are positive regulators of basal defense. AtOZF1 interacts with NHL3 and VDAC2 in plasma membrane and mitochondria, respectively. Our results demonstrate that AtOZF1 coordinates multiple steps of plant-pathogen interaction.