This study aims to examine the effect of firm size on tax avoidance and profitability as a moderating variable in the Egyptian companies. To achieve this goal, the study relied on a sample of 90 listed non-financial Egyptian companies, with 1080 firm-year observations between years 2010-2021. In order to test hypotheses, three indicators to measure profitability were used; Return on assets, Return on equity and Earnings per share in addition to three indicators to measure tax avoidance were used, The difference between statutory tax rate and effective tax rate, Book-tax difference (as a typical scale for the company's tax avoidance level), and cash effective tax rate (as an inverse scale). The study also used total assets as an indicator for firm size. The effects of operating cash flow, leverage, inventory intensity and capital intensity were controlled. The results indicated that there was a positive relationship between firm size and tax avoidance measured by BTD, and no relationship between firm size and tax avoidance measured by TA and CETR. Profitability (measured by ROA, ROE, EPS) had a significant positive effect on the relationship between firm size and tax avoidance (measured by TA and CETR). There was also a significant negative effect for profitability measured by EPS on that relationship when tax avoidance was measured by BTD, while profitability showed no effect when measured by ROA and ROE on that relationship when tax avoidance was measured by BTD. These results represented an empirical support for the political power theory.