Scaling in membrane distillation (MD) is a key issue in desalination of concentrated saline water, where the interface property between the membrane and the feed become critical. In this paper, a slippery mechanism was explored as an innovative concept to understand the scaling behavior in membrane distillation for a soluble salt, NaCl. The investigation was based on a novel design of a superhydrophobic polyvinylidene fluoride (PVDF) membrane with micro-pillar arrays (MP-PVDF) using a micromolding phase separation (μPS) method. The membrane showed a contact angle of 166.0 ± 2.3° and the sliding angle of 15.8 ± 3.3°. After CF4 plasma treatment, the resultant membrane (CF4-MP-PVDF) showed a reduced sliding angle of 3.0°. In direct contact membrane distillation (DCMD), the CF4-MP-PVDF membrane illustrated excellent anti-scaling in concentrating saturated NaCl feed. Characterization of the used membranes showed that aggregation of NaCl crystals occurred on the control PVDF and MP-PVDF membranes, but not on the CF4-MP-PVDF membrane. To understand this phenomenon, a “slippery” theory was introduced and correlated the sliding angle to the slippery surface of CF4-MP-PVDF and its anti-scaling property. This work proposed a well-defined physical and theoretical platform for investigating scaling problems in membrane distillation and beyond.