The Rio Del Rey Basin in Cameroon develops mudstone diapirs. Due to the control of mudstone diapirs， oil and gas reservoirs of fault blocks and fault anticlines are developed in the shallow strata of the basin and enter into the middle and late stages of development. The success rate of exploratory wells in middle-deep layer S5 is low， and resource replacement is facing challenges due to poor previous research and insufficient understanding of oil and gas accumulation law. The regional sedimentation， structures，and hydrocarbon accumulation characteristics， especially the balanced profile of regional tectonic evolution， were researched，and it was found that mudstone diapirs in the Rio Del Rey Basin were derived from the thick Akata mudstones of the Paleocene series in the deep part， and their activity time began from the end of Eocene to present. It locally controlled the deposition ranges of the sand body in the front of the S5 delta in the early Miocene. Sand bodies， mudstone diapers， and associated faults were easy to form structural-lithological and fault-block traps， which were formed earlier than the oil-generating period of Akata mudstone.Mudstone diapirs and faults provided channels for oil and gas migration， and the combination of source-reservoirtransportation-accumulation was conducive to hydrocarbon accumulation around mudstone diapirs in S5. However， the reasons for the drilling failure of S5 were analyzed in the basin， and there were differences in oil and gas accumulation characteristics around mudstone diapirs. Oil and gas easily escaped upward along the activity channel of mudstone diapirs due to the long-term activity of mudstone diapirs and its penetration into S5， resulting in poor preservation conditions for the first row of structural-lithological traps directly contacting mudstone diapirs and thus making hydrocarbon accumulation difficult. Previous drilling in multiple exploratory wells on the first row of structural-lithological traps also failed. The second row of structural traps （two-step structural belt） controlled by mudstone diapirs could be trapped by updip faults， which were not affected by the later activity of mudstone diapir， and they became favorable places for oil and gas enrichment in S5. On this basis， Sinopec successively deployed two exploratory wells in the second row of structural belts from 2018 to 2023， and oil discovery reached a commercial level， which further confirmed the control effect of mudstone diapirs on middle-deep hydrocarbon accumulation in the Rio Del Rey Basin， and it proved that the twostep structural belts under the control of mudstone diapirs were favorable exploration belts in the future.