To encourage the utilization of low-quality palm oil with high free fatty acid and moisture content (>0.1 wt%), a novel catalyst with two spatial shells and different active sites, double-shelled hollow mesoporous silica incorporated copper (II) (Cu/DS-HMS-NH 2 ), is fabricated via the two-stage hydrolysis and condensation technique. The influence of four parameters (eg, catalyst loading, temperature, reaction time, and the mass ratio of methanol to degummed palm oil (DPO)) on the yield of fatty acid methyl ester (FAME) are monitored and optimized using a combination of response surface methodology (RSM)and face centered-central composite experimental design (CCF-CCD). The optimized FAME yield is predicted at 86.63 wt% and experimentally obtained at 87.14 ± 0.11 wt% (FAME purity of 98.45 ± 0.67 wt%) under the following optimum condition: 55.3 C, 5 h, methanol to DPO mass ratio of 5.3:1, and 5 wt% catalyst loading. The experimental and predicted values are proportional and in direct agreement with an error of 0.51%. The goodness of fit analysis also indicates conformity between the mathematical model and the experimental results. The reusability study shows that Cu/DS-HMS-NH 2 is stable until the fifth run, evident from the yield of FAME which stays above 80%. These results prove the potential utility of Cu/DS-HMS-NH 2 for the direct conversion of low-quality vegetable oils to biodiesel without any pre-treatment.