The geological structure of the beibu gulf basin oilfields in west Nanhai is complex. Down-hole incidents are frequent in well drilling and completion. In order to cope with the increasing difficulties in the marginal oil field drilling, such as wellbore collapse, multiple faults, formation leak, drill pipe sticking, difficult reserve protection, etc. in the Weizhou formation in this area, a novel full oil-based drilling fluid formula was developed through laboratory compatibility experiments based on the ratio of each drilling fluid component. Comparison of full oil-based drilling fluids with conventional oil-based drilling fluids indicate that the full oil-based drilling fluids have stronger sealing and plugging, inhibition, good lubrication performance, strong anti-pollution ability, good wellbore cleaning and good reservoir protection. It can also effectively increase ROP and solve many problems with the conventional oil-based drilling fluid, achieving a comprehensive drilling efficiency.