As a major life trauma, COVID-19 had negative impacts on psychological well-being. The aim of this study was to test and verify the mediation of resilience, hope and self-efficacy and to analyze the moderating effect of gender and COVID-19 contagion on the association between symptoms of anxiety, stress and depression, and post-traumatic growth among adults during COVID-19. A cross-sectional study was conducted via an online survey with self-administered questionnaires. The Depression, Anxiety, and Stress Scale, the Post-traumatic Growth Inventory, the Resilience Scale, the General Self-Efficacy Scale, and the Comprehensive State Hope Scale were used. A total of 493 (n = 262 female and n = 231 male) participated in the survey (Mage= 33.40 years, SD = 13.41, range = 20 to 60). A multiple mediation model was used to verify the mediating effect of resilience, hope and self-efficacy on the relationship between symptoms of anxiety, stress and depression, and PTG. A moderated mediation model was examined to find and test the moderated effects of gender and COVID-19 contagion on the mediation model. Results showed the indirect effects of anxiety (β = 0.340 (0.120); 95% CI [from 0.128 to 0.587]) and depression (β = 0.222 (0.095); 95% CI [0.048, 0.429]) on PTG trough resilience and hope. Symptoms of anxiety, stress and depression, and self-efficacy were significantly highest in females. Moreover, males and participants with COVID-19 contagion had significantly higher levels of resilience and post-traumatic growth. These findings suggest that hope and resilience, as protective factors, could be an important key to developing an intervention strategy to enhance and improve psychological health during a crisis.