The human group X secreted phospholipase A2 (hGX sPLA2) induces lipid droplets (LD) accumulation, accelerates fatty acid (FA) oxidation and induces changes in cell signaling in the highly tumorigenic MDA-MB-231 breast cancer cells. These changes protect the cells from serum withdrawal-induced cell death. Oleic acid (OA), which is one of the main products of hGX sPLA2 enzymatic activity, shows similar effects on LD formation and MDA-MB-231 cell survival. Here we show that hGX sPLA2 and OA promote MDA-MB-231 cell survival also during other types of metabolic stress. We found that the presence of glucose in the medium is necessary (and sufficient) for the pro-survival effects of hGX sPLA2. Using flow cytometry, we found that hGX sPLA2 and OA display diverse, even opposing effects on different cancer cells. hGX sPLA2 and OA induced LD accumulation in CaCo-2 colorectal cancer and SH-SY5Y neuroblastoma cell lines, but failed to reduce starvation-induced cell death. Surprisingly, hGX sPLA2 even reduced LD accumulation in a dense culture of HeLa cervical cancer cells, whereas OA had no effect. Our results suggest that the effects of hGX sPLA2 on LD metabolism and the role of LDs in cell survival during stress are diverse and depend strongly on the specific characteristics of the cancer cell type in question.