BackgroundMembrane distillation (MD) is considered a viable technology to overcome the issue of water scarcity by desalination of seawater. However, the application of MD has been severely restricted by membrane‐wetting phenomena. This study aims to optimize the desired mixed matrix hollow fiber (HF) membrane conditions that have anti‐wetting characteristics for efficient desalination. Response surface methodology (RSM) based on central composite design (CCD) was used to predict and optimize the permeate flux and salt rejection. The Combined effects of polymer (polyvinylidene fluoride, PVDF) concentration, nano‐fumed silica (NFS) particle loading, coagulation bath temperature (CBT), and air gap distance (AG), as well as their interactions in terms of desalination performance, have been investigated.ResultsThe linear factors (NFS, CBT), the quadratic effects of all variables, as well as the interacting terms between (PVDF, NFS), (PVDF, CBT), and (NFS, CBT) had significant effects for both pure water and permeate fluxes (PWF, PF). For salt rejection (SR), only PVDF presented a linear effect, while a quadratic effect was obtained in (NFS, AG) and an interaction effect was obtained between PVDF and NFS. Under optimal conditions of PVDF (15.03 wt.%), NFS (1.21 wt.%), CBT (54.85 oC), and AG (9.9 cm), the optimal mixed matrix HF membrane demonstrated higher experimental average values for pure water and permeate fluxes reached up to 11.95 and 11.61 kg m−2 h−1 respectively, and an SR of 99.96% as compared to the pristine membrane.ConclusionOur research provides an efficient anti‐wetting NFS/PVDF mixed matrix HF membrane, indicating that the optimal membrane possesses a high potential for the direct contact membrane distillation (DCMD) process.This article is protected by copyright. All rights reserved.