Based on the limitation of visual working memory, interference suppression is one of abilities to keep attentional resources on targets rather than distractor items. There was still a controversy on how the mechanism of interference suppression optimized visual working memory, which was derived from distinct paradigms. Change detection combined systematic lateralization task was proposed to solve this controversy. Therefore, this study aimed to explore the attentional processing and its potential mechanism of target and distractor items through the new paradigm. The behavioral results indicated significantly higher accuracy and shorter response times for targets when the distractor was horizontal compared to vertical. For the ERPs results, the N2pc component (223~273 ms) exhibited a more negative amplitude contralateral to the target than ipsilateral in the target lateral condition. Conversely, the latency of N2pc was longer ipsilateral to the target than contralateral. In the distractor lateral condition, moreover, the amplitude of Pd at the electrodes contralateral of distractor was more positive than at the electrodes ipsilateral. However, no significant difference was found in Pd latency. Analysis of difference waves revealed that the N2pc amplitude was more negative in target lateral conditions compared to distractor lateral conditions, while the distractor lateral condition elicited a stronger Pd component. No significant latency differences were observed in either N2pc or Pd difference waves. In conclusion, this study supported the signal suppression hypothesis that active suppression processing prevents distractor items from capturing attention, even if it produces a priority signal of ”attended to me”.