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Background: Lung cancer patients have the highest risk for developing depression amongst all cancers. Hopelessness is a known predictor of depression. Previously, social support was found to lower hopelessness and depression symptoms in breast cancer patients. These results have yet to be replicated with other types of cancer. This study tested hopelessness, social support, and their interaction as predictors of depressive symptoms in patients newly diagnosed with stage IV non-small cell lung cancer (NSCLC). Methods: Patients with stage IV NSCLC (N=186) completed self-report measures for hopelessness (BHS), social support (SNI and marital status), and depression (PHQ-9 at diagnosis. Depression was assessed again months later. Spearman correlations examined the relationship amongst predictor (hopelessness, SNI, marital status), covariants (age, income, employment), and outcome (depression) variables. For each measure of social support, a multiple regression tested baseline hopelessness, social support, and their interaction as predictors of depression at baseline and four months while controlling for the relevant covariates. Baseline depression included with the follow-up regression to compare scores. Results: About half the patients scored for mild depression (M = 6.37, SD = 5.22) and mild hopelessness (M = 4.27 SD = 3.26) at baseline. After a correlational examination, only income was found to be significantly associated with baseline depression (p<0.05). Marital status had no significant effect on hopelessness or depression at either time points. At baseline, hopelessness was a significant predictor in marital status (p = 0.02) and SNI (p<0.001) models. The interaction between SNI and hopelessness was significant for predicting depression at 4-month follow-up (p<0.05). Low social support was associated with higher scores of hopelessness and depression after controlling for relevant covariates. Depression scores were unchanged for patients with medium to high social support despite their degree of hopelessness. Discussion: Social support moderates the relationship between hopelessness and depression in NSCLC patients. With this in mind, medical staff should monitor hopelessness symptoms and recognize their role as patients’ support system as to promote successful prognosis.