To investigate the mechanism by which fibroblast growth factor 2 (FGF‐2) inhibits apoptosis in the human small cell lung cancer cell line H446 subjected to serum starvation, apoptosis was evaluated by flow cytometry, Hoechst 33258 staining, caspase‐3 activity, and DNA fragmentation. Survivin expression induced by FGF‐2 and protein kinase Cα (PKCα) translocation was detected by subcellular frac‐tionation and Western blot analysis. In addition, FGF‐2‐in‐duced release of Smac from mitochondria to the cytoplasm was analyzed by Western blotting and immunofluorescence. FGF‐2 reduced apoptosis induced by serum starvation and up‐regulated survivin expression in H446 cells in a dose‐dependent andtime‐dependentmanner, andinhibitedcaspase‐3 activity. FGF‐2 also inhibited the release of Smac from mitochondria to the cytoplasm induced by serum starvation and increased PKCα translocation from the cytoplasm to the cell membrane. In addition, PKC inhibitor inhibited the expression of survivin. FGF‐2 up‐regulates the expression of survivin protein in H446 cells and blocks the release of Smac from mitochondria to the cytoplasm. PKCα regulated FGF‐2‐induced survivin expression. Thus, survivin, Smac, and PKCα might play important roles in the inhibition of apoptosis by FGF‐2 in human small cell lung cancer cells.