During well testing and killing operations, tubing couplings with a larger diameter than the tubing body significantly increase the flow friction in the casing-tubing annulus, alter the rheological behavior of the kill fluid, thereby affecting operational accuracy and even leading to operational failure in severe cases. Most existing relevant studies focus on the impact of changes in flow area on flow, but ignore the effect of the coupling’s own structural configuration. Moreover, the research conclusions lack verification by downhole measured data, and there is an urgent need to further improve the analysis accuracy. Taking an ultra-deep well in the Xinjiang Oilfield as the engineering background, this paper conducts targeted research: first, a physical model of the flow field in the casing-tubing annulus passing through the tubing coupling is established, and a method for judging and determining the rheological properties of the kill fluid based on the fitting of the physical model and key parameters is proposed; on this basis, a numerical model including the coupling’s structural configuration is established and solved, and the friction calculation equation for the casing-tubing annulus passing through the tubing coupling is obtained through nonlinear fitting; finally, the calculation results of this equation are compared and verified with the measured data and numerical simulation results. The research results show that: under six working conditions, the flow characteristics of the kill fluid all conform to the characteristics of Bingham fluid, which is also consistent with the general flow regime of kill fluid flow; comparing the numerical analysis results of the target well in the Xinjiang Oilfield with the calculation results of the fitting equation, the maximum error, minimum error, and average error of friction analysis under the six working conditions are 14.46%, 0.39%, and 6.15% respectively; the total friction of the casing-tubing annulus in the entire well section calculated based on the theoretical equation is 12.085 MPa, and the relative error compared with the field measured 13 MPa is 7.57%, which meets the engineering accuracy requirements. The equation proposed in this study provides a universal equation for predicting the pressure drop of non-uniform flow in the wellbore, and also has an important reference value for predicting the wellbore pressure in drilling and oil-gas production operations.