Abstract: Well MaHW1602 in Mahu Oilfield owns complex formation conditions, the target layer in the Triassic Baikouquan Formation contains hard mudstone and loose conglomerate, and downhole events such as collapse and caving are prone to occur during horizontal section drilling. Due to the insufficient collapse resistance of the " desulfurization” drilling fluid applied in this area in recent years, through analyzing the formation characteristics and the challenges in drilling fluids, the activity modifier, plugging agent and inhibitor were preferably selected in the laboratory, and the non-sulfonated low-activity drilling fluid system was further developed. The results of indoor test show that the plugging rate of low-activity drilling fluid exceeds 90%, and the average water activity is 0.863, which meets the requirements of field drilling. The drilling fluid was applied in the third spud section of Well MaHW1602, there was no obvious hole enlargement in the loose and collapsing-prone section, the wellbore was regular, and the average hole enlargement rate was 6.5%. In addition, there was no obvious weight stacking during drilling, the electrical logging and casing RIH were performed smoothly without any problems such as the rapid changes in drilling fluid properties, lost circulation during RIH or pump starting, etc. Research and field application suggest that the low-activity drilling fluid has good plugging and anti-sloughing properties, which can meet the requirements for safe drilling of long lateral horizontal wells in the Mahu Oilfield.