Background and aim: The survival of children with chronic disease has increased in recent years, and focusing on their quality of life, instead of immediate interventions is recommended. This cross - correlation study was conducted to determine the relationship between spiritual attitude and hope with the quality of life of adolescents with chronic disease and special needs.Methods: The research population consisted of 134 adolescents with chronic disease and special needs, who were hospitalized in different wards of or visited in clinics of the Children’s Medical Center, the Cancer Institute, the Mofid and the Masih Daneshvari hospitals.134 adolescents were selected using the convenience sampling method and based on the inclusion criteria of the study. The data collection tools included "the Demographic Characteristics Questionnaire", "Adolescents’ Spiritual Attitude Scale", "Adolescents’ Hope Scale" and "Children’s Quality of life Checklist". The reliability and validity of these scales were examined. The data were analyzed with the SPSS19 software using descriptive tests, the Spearman correlation coefficient and regression analysis.Findings: In this study, 134, 13-18 years old adolescents with chronic disease were studied with a mean±SD age of 15.03±2.03. The majority of the research samples (56.7%) were male. The majority of the samples (41%) were adolescents with chronic respiratory disorders, who were hospitalized in the wards. Aaverage spiritual attitude was 163.8±45.21 for boys and 166.52±27.17 for girls. The mean of hope was 83.61±17.8 in boys and 8383±18.8 in girls, and the average quality of life was 62.05±16.16 in boys and 67±15.02 in girls.There was not significant relationship between the study variables and sex, but there was negative significant relationship between age and spiritual attitude (r=-0.245, p<0.05). Spiritual attitude (p<0.05, r=0.184), and hope (p<0.05, r=0.176) had a significant positive relationship with the quality of life. There was also a significant positive relationship between spiritual attitude and hope (p<0.05, r=0.406). The regression analysis showed spirituality, kind of admission and father education, can explain 14/6% of the changes in the quality of life.Conclusion: The findings indicates that issues such as purposefulness in life, belief in God, and optimism, as constituents of spiritual attitude and hope, can improve the quality of life of adolescents with chronic disease.