The main purpose of this study is to examine the factors affecting the three different profitability ratios (gross profit, interest depreciation and tax profit and net profit) of the firms operating in the manufacturing sector traded on Borsa Istanbul (BIST) and determine the effect levels of these ratios. For this purpose, the relationship between profitability ratios and financial indicators such as liquidity ratios, financial structure ratios, activity efficiency ratios, stock market performance ratios and growth rates and in addition to the fact that it was audited by Big 4 audit offices, auditor gender and non-financial factors such as positive opinion was analyzed were analyzed. For this purpose, the financial and annual reports of the manufacturing industry enterprises traded in BIST between the years 2005-2015 were calculated and the panel data were examined with the regression analysis. According to the findings of the research, various financial ratios and other factors that affect the profitability types of enterprises are found to be significant. The most important ratios which effects the profitability ratios of the enterprises are the liquidity ratios, Altman Z-Score, financial leverage ratio, auditing by Big 4 audit offices, tangible asset turnover and return on assets. Factors affecting the profitability include, operating cash flow ratio, auditor gender, interest the positive opinion, price to earning raito, market value to book value and earnings per share. Other effective rates on profitability were determined as receivables turnover, intangible asset turnover, interest coverage ratio. Asset growth rate has no effect on profitability.