Objective To explore the influencing factors of job burnout among nurses in level 2 and level 3 hospitals in Guangdong province. Methods A total of 2 066 first line nurses from 133 medical, surgical and intensive care units (ICU) of 23 level 2 and level 3 hospitals in Guangdong province were surveyed employing the questionnaire Hospital Nursing Human Resources Research during December 2013 to August 2014. Results In the multivariate logistic regression models, each additional doctor per nurse was associated with 1.34 times increase in the likelihood of high level of emotional exhaustion(EE). Nurses had a 57.4%higher risk of high level of EE when they worked overtime. Every one point increase in ancillary service score, and every one more year working as a nurse was associated with 5.4%, 2.3%increase in the likelihood of high level of EE, respectively. Nurses were 42.1%,40.9%more likely to exhibit high level of depersonalization(DP) when they worked in medical units or hospitals of level 3, compared with nurses of surgical units and hospitals of level 2. Nurses had a 29.5%higher risk of high level of DP when they worked overtime. Nurses holding higher positions had a lower likelihood(37.7%) of high level of reduced personal accomplishment(PA) compared with nurses holding lower positions. Nurses in medical units or ICUs had a 31.2%, 51.6%higher risk of high level of PA than nurses in surgical units, respectively. Conclusions Job burnout of nurses is at a quite high level in level 2 and level 3 hospitals in Guangdong province. The probability of the occurrence of burnout is related to the hospital, unit and nurse characteristics and nursing workloads.