This study aims to analyze the effect of spread profit-sharing, fee-based income, BOPO and financing to deposit ratio to profitability (a case study on Sharia Commercial Banks in 2010-2016). The data used in this study are quarterly data during the period of 2010-2016. This research is an associative descriptive research to see the correlation between one variable with the others. The data used are secondary data obtained from quarterly financial reports published by the financial services authority. The type of this research is quantitative research using multiple linier regression data analysis method. The data processing uses SPSS software version 21. The result of the research shows that the variable of spread profit-sharing and fee-based income have positive and significant effect to profitability, while the variable of BOPO and financing to deposit ratio have a significant negative effect on profitability at Sharia Commercial Banks. Simultaneously, the variable of spread profit-sharing, fee-based income, BOPO and financing to deposit ratio have positive and significant influence to the profitability of the Sharia Commercial Banks. The coefficient of determination adjusted R2 indicates that the variable of spread profit-sharing, fee-based income, BOPO and financing to deposit ratio influence profitability by 53.8% while the remaining 46.2% influenced by other factors not examined in this study.