Abstract Background The global COVID-19 pandemic is still not under effective control, and strong workplace supports with comprehensive mental health interventions are urgently needed to help medical staff effectively respond to the pandemic. This study aimed to verify the effect of an online resourcefulness training program on the resourcefulness, and psychological variables of front-line medical staff working in the COVID-19 isolation ward. Design A pre-test and post-test quasi-experimental design with control group was employed. Participants A total of 60 participants working in two isolation wards were recruited via convenience sampling. The two isolation wards were randomly assigned to the control group (isolation ward 1, n = 30) and the intervention group (isolation ward 2, n = 30). Intervention The participants were trained online by video conferences and WeChat. The control group received conventional training (e.g., psychological training, psychological counseling), while the intervention group received a 4-h online resourcefulness training. Both groups learned updated guidelines of COVID-19 simultaneously via video conference. The primary outcomes (resourcefulness, anxiety, depression and coping styles) and the secondary outcome (psychological resilience) were measured before intervention and three time points after intervention. Results After the intervention and one week after the intervention, the resourcefulness, resilience, and positive response scores of the participants in the intervention group were significantly higher than those of the control group. The anxiety and negative response scores in the intervention group were significantly lower than those of the control group (all p