Dental cast alloys have been widely used in modern dental restoration. However, due to oral complex environment and individual differences, continuous corrosion of alloys occurs. As a result, metal ions like nickel ion (Ni3+) can be released from alloys for prolonged time. This can lead to chronic adverse effects on the surrounding tissues and cells. In order to evaluate the cytotoxic effects of nickel ion on human gingival fibroblasts and explore the mechanism, we observed the effects of the ion salt solution on the proliferation of cultured cells in vitro. The IC50 value of Ni3+ was 389.6 μmol/l. Then we studied the mechanism of inhibition proliferation of Ni3+ on cultured cells by flow cytometry, the results have shown that Ni3+ induced apoptosis of cultured cells with the pretreatment process prolonged. Besides, we also detected the expression level of cysteinyl aspartate specific protease-3 (caspase-3) mRNA which was shown activated. As a conclusion, the inhibition effect of Ni3+ on the proliferation of gingival fibroblasts was partly due to its potential of inducing apoptosis, and the mechanism of apoptosis is via the caspase-3 activation. The further studies will be fulfilled by animal experiment or evidence-based medicine method.