This paper discussed the influence mechanism of challenge and hindrance stressors on employee’s creativity based on the two-dimensional structure of stress, focusing on the mediating effect of creative self-efficacy and the moderating effect of supervisor-subordinate guanxi. We selected the enterprise’s employees and their direct supervisor as research subjects and analyzed the 336 sets of paired data through hierarchical regression, and so forth. The results indicated that challenge stressors had a significantly positive effect on employee’s creativity while hindrance stressors had remarkable negative influence on employee’s creativity; creative self-efficacy played a partially mediating role in the relationships between challenge and hindrance stressors and employee’s creativity; supervisor-subordinate guanxi negatively moderated the relationship between challenge stressors and employee’s creativity; at the same time, supervisor-subordinate guanxi positively moderated the relationship between hindrance stressors and employee’s creativity.