Background: According to the World Health Organization (WHO), depression is a common mental health illness that is characterized by a persistent feeling of sadness and loss of interest. The present study examined the association of two mental health variables (i.e., depression, anxiety) with quality of life (QoL), and the socio-demographic characteristics of Afghan women living under the rule of Taliban government in Afghanistan. Methods: A cross-sectional study was administered across major provinces of Afghanistan (Herat, Mazar-e-Sharif, Kabul, and Samangan). Logistic regression models were used to examine the association of depression, anxiety with QoL and socio-demographic characteristics among women (N=465). Results: The prevalence of depression symptoms were 80.6%, and mild to extremely severe anxiety was 81.3%. Depression symptoms among Afghan women were associated with being older, having more children, lower education level, other individuals’ bad behavior, traumatic events, and feeling physically ill. Multiple regression analysis indicated that poor physical domain of quality of life (aOR:4.3; 95%CI: 1.748-11.029, p=.002), and poor psychological domain of quality of life (aOR:22.168; 95%CI: 7.50 – 65.49, p<.001) were significantly associated with depression. Conclusions: The prevalence of depression was high women living under the government of the Taliban in Afghanistan. Considering the high prevalence of depression, anxiety, and their impact on quality of life and the overall quality of healthcare services, international health organizations should implement programs for regular screening of depression and anxiety, and there should be psychological counselling services available for vulnerable women living under the government of the Taliban. Keywords: depression, anxiety, quality of life, women, Taliban, Afghanistan