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Purpose: Cancer and its treatments can cause complex issues including physical, psychological and spiritual aspects. We aimed to examine the impact of cancer to the spirituality well-being, quality-life and depression among cancer patients in eastern part of Indonesia. Methods: Our study was conducted between January-April 2018 among a sample of 100 cancer patients (stadium III and IV) who admitted to a curative setting in the regional public hospital. All the participants filled three self-report questionnaires; the Spirituality Well Being Scale, the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QOL), and the Beck Depression Inventory in addition to socio-demographic data. Pearson correlation was conducted to examine the associations between spirituality and depression, overall quality of life and quality of life domains (functional and symptoms). Result: All of the participants (n=100) are affiliated with particular religions and most of them always conduct worships. Pearson correlation showed significant positive associations between spirituality and overall QOL (p < 0.01) and individual functional quality of life domains (physical, roles, emotional, and social). Spirituality was negatively associated with symptoms domains (fatigue, pain, dyspnea, insomnia, loss of appetite and financial difficulties). Higher spirituality was associated with lower depression (p < 0.01). Conclusion: This study confirm that spirituality related with overall quality of life and depression and this reiterates the importance of developing spirituality-based intervention along with cancer care for this population.