This study examined the gender difference regarding the simultaneous impacts of Job Demands-Control-Support model variables (job demands, job control, supervisor support, and coworker support) on job satisfaction via work-family conflict using multiple group structural equation modeling. The participants were 1,092 male and 1,367 female employees from the 2008 National Study of the Changing Workforce. Results showed that job control was only significantly associated with work-family conflict in female employees. In addition, high levels of job control, supervisor support, and coworker support were significantly associated with an increase in job satisfaction in both male and female employees. Regarding the mediating effect, work-family conflict mediated relationships between job demands, supervisor support, coworker support, and job satisfaction in both male and female employees, whereas work-family conflict only mediated the association between job control and job satisfaction in female employees. In this study, the implications considering the gender difference and workfamily contexts are discussed.