By coupling heat and mass transfer for C3H8–n-C4H10-CO2-heavy oil systems as well as by treating heavy oil as multiple pseudocomponents, a new method and its computational scheme has been developed to determine individual diffusion coefficients of alkane solvents and CO2 in heavy oil at high pressures and elevated temperatures by dynamic volume analysis (DVA). Experimentally, well-designed diffusion tests have been conducted for an n-C4H10-heavy oil system, a CO2-heavy oil system, an n-C4H10-CO2-heavy oil system, and a C3H8–n-C4H10-CO2-heavy oil system by using a visualized PVT setup, respectively. The volume change of liquid phase is monitored and recorded during the measurements, while the gas chromatography method is employed to determine the compositions of gas mixtures at the beginning and the end of the diffusion tests, respectively. Theoretically, the volume-translated Peng-Robinson equation of state with characterizing heavy oil as multiple pseudocomponents has been incorporated to develop a two-dimensional heat and mass transfer model for the aforementioned systems. The alternating direction implicit (ADI) algorithm is applied to solve the two-dimensional difference equations into which a moving gas-liquid interface has been successfully incorporated. The discrepancy between the measured and calculated dynamic volume change and the discrepancy between the measured and calculated gas compositions at the end of diffusion tests have been minimized to determine the individual diffusion coefficients. Alkane solvents diffuse faster than CO2 in heavy oil, while addition of alkane solvent(s) into CO2 stream not only enhances mass transfer, but also achieves an improved swelling effect of heavy oil. Among the four diffusion tests, the largest dynamic swelling factor at the end of diffusion test is measured to be 1.118 for the C3H8–n-C4H10-CO2-heavy oil system.