PET/PA6, hollow, segmented-pie, microfiber nonwovens (PET/PA6 HSMNs) play an important role in a microfiber, synthetic leather base. Most of the current PET/PA6 HSMNs generally lack in hygiene performance. Moreover, there is an urgent need for the asymmetric wettability of PET/PA6 HSMNs to ensure the comfort of clothing. In this work, a novel, asymmetrically wettable, PET/PA6 HSMN with a gradient structure is proposed, which can regulate liquid adsorption and directional transport. An MOF-303 was successfully synthesized and loaded onto the PET/PA6 HSMN, which had been pre-treated with gradient hydrolysis under sulfuric acid. The droplet quickly permeated the modified PET/PA6 HSMN, and the droplet disappearance time decreased to 62.40 ms. The liquid strikethrough time of the modified PET/PA6 HSMN reached 5.16 s. The maximum adsorption capacity of the modified PET/PA6 HSMN was 68.161 mg/g, which was improved by 122.83%. In addition, the air permeability of the pre-treated PET/PA6 HSMN increased from 308.70 mm/s to 469.97 mm/s, with the sulfuric acid concentrations increasing from 0% to 20%, and the air permeability of the modified PET/PA6 HSMN decreased gradually from 247.37 mm/s to 161.50 mm/s. Furthermore, the tensile strength of the modified PET/PA6 HSMN treated with sulfuric acid and MOF-303 was also obviously enhanced compared with the PET/PA6 HSMN treated with pure sulfuric acid. This PET/PA6 HSMN, with asymmetric wettability, owing to its high hygiene performance and water transport capabilities, is promising and able to extend the application of a microfiber synthetic leather base for clothing.