Advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy experience functional decline and decreased quality of life. The purpose of this study was to evaluate the effects of a web-based health education program on global quality of life, quality of life-related functional dimensions, and symptom distress of initially diagnosed advanced non-small cell lung cancer patients. This study used a randomized, pre- and post-repeated measures design. A total of 55 participants were randomly assigned to an experimental group (n = 27) and a control group (n = 28). The experimental group participated in a web-based health education program, and the control group received usual care. Patients were assessed at 4 time points: baseline assessment (T0), and then 1, 2, and 3 months (T1, T2, and T3) after participating in the web-based health education program or receiving usual care. Patients in the experimental group had significantly greater global quality of life and emotional function, and significantly less top ten significant symptom distresses compared to those in the control group. There were no differences between the groups and within groups with respect to physical function, role function, cognitive function, and social function. The web-based health education can improve global quality of life, emotional function, and top ten significant symptom distresses in patients receiving chemotherapy during the first 3 months after initial diagnosis of advanced NSCLC. Web-based health education can improve quality of life and lessen distress of initially diagnosed NSCLC patients treated with chemotherapy.