Abstract: In the tight heavy oil reservoirs with ultra-low permeability in Ma 56 block, Santanghu Oilfield, to address the issue of low recovery rate brought by depleted development, a pilot CO₂ huff-n-puff test was conducted. By analyzing the factors influencing CO₂ huff-n-puff, well screening principles were determined based on reservoir conditions, formation conditions, well dynamics, and wellbore conditions. On the basis of analyzing the mechanisms of CO₂ huff-n-puff during the seven stages from injection to stabilized production, by combining numerical simulation and field tests, aiming at the optimal oil increment and oil change rate of a single well, and under the conditions of emphasizing the influence of CO₂ miscibility and supercritical state, rational injection parameters for gas huff-n-puff were further determined, that is, an injection of 2 000 tones of liquid CO₂ into a single well in a single round, with an injection rate of 100 t/d, soaking period of 20 days, and a maximum huff-n-puff rounds of three. The CO₂ huff-n-puff technology was applied in six wells in the ultra-low permeability tight heavy oil reservoir in Ma 56 Block, achieving a 100% success rate with an average single-well oil increasement of 1 073 tones and a cumulative oil increasement of 6 440 tones. Notably, Well Ma 56-7H achieved an oil increasement of 1 267 tones even after multiple rounds of fracturing and water huff-n-puff. The research outcomes provide a new pathway for further enhancing recovery rate in ultra-low permeability tight heavy oil reservoirs developed by depleted pattern.