Abstract: Through the long development processes of reservoir sedimentation and diagenesis, acidic and alkaline fluids play key roles in controlling deep reservoir development. However, the ways in which deep fluids control and transform the reservoir under complex fault conditions remain unclear. In this study, a 2D model was established based on a typical sub-salt to intra-salt vertical profile in the Qaidam Basin, China. Based on measured data, multiphase flow reaction and solute transport simulation technology were used to analyze fluids flow and migration in the intra-salt and sub-salt reservoirs, determine the mineral dissolution, precipitation, and transformation in the reservoir caused by the deep fluids, and calculate the changes in reservoir porosity. Results show that deep fluid migrates preferentially along dominant channels and triggers a series of fluid–rock chemical reactions. In the first stage, a large amount of anhydrite precipitated in the fault as a result of upward migration of deep saline fluid, resulting in the formation of anhydrite veins and blockage at the base of the fault. In the second stage, organic acids caused minerals dissolution and a vertical channel was opened in previously blocked area, which promoted continuous upward migration of organic acids and the formation of secondary pores. This study clarifies the transformative effects of deep alkaline and acidic fluids on the reservoir. Moreover, the important fluid transport role of faults and their effect on reservoir development were determined.