Abstract: Objective To discuss the effect and differences of deficient and sufficient folic acid (FA) on the telomere length and genome stability of normal human skin cells and malignant skin cells. Methods Normal human fiber cell line BJ and malignant melanoma cell line A375 were cultured in the medium containing different concentration of FA（30-3 000nmol/L）for 21d to test the absolute telomere length (aTL) using improved method of RT-qPCR. Genome stability was evaluated by chromosome instability (CIN) indexes, CBMN-Cyt. Results At FA 30nmol/L, the telomere length of BJ cells presented abnormal growth or shortening with the extension of intervention time, and chromosomal instability(CIN) rate was significantly decreased (P<0.05); at FA 100-300nmol/L, the telomere length and CIN rate appeared positive correlation with FA concentration; at FA 1 000nmol/L, the telomere length and CIN rate remained stability. At FA 30-3000nmol/L, the telomere length of A375 cells showed a trend of increase in 15d while shortening in 21d (P<0.05); at FA 30nmol/L, CIN rate were significantly increased (P=0.013). Conclusion The changes of telomere length and genome stability of A375 cells do not significantly depend on folic acid. FA deficiency in BJ cells would induce the abnormal telomere length and genome instability.