Using the statistical approach, this work seeks to optimize the process parameters to boost the generation of an organic solvent-tolerant lipase by Staphylococcus capitis SH6. The main parameters influencing the enzyme production were identified by using Plackett–Burman’s screening design. Among the test variables, only tryptone (25 g/L), malt extract (2.5 g/L), NaCl (10 g/L) and pH (7.0) contributed positively to enzyme production. Then, the crude lipase was immobilized by adsorption on CaCO₃ at pH 10. A maximum immobilization efficiency of 82% was obtained by incubating 280 mg of enzyme with CaCO₃ (1 g) during 30 min. The immobilized lipase was more stable toward organic solvents than the free enzyme. It retained about 90% of its original activity in the presence of ethanol and methanol. After that, the immobilized enzyme was used for biodiesel production by transesterification process between waste oil and methanol or ethanol during 24 h at 30 °C. Our results show that the lipase can be utilized efficiently in biodiesel industry. Likewise, we have demonstrated that the immobilized enzyme may be implicated in the biodegradability of waste grease; the maximum conversion yield into fatty acids obtained after 12 h at 30 °C, was 57%.