The change of intracellular free Ca²⁺ in A₅₄₉ cells sensitive and A₅₄₉/DDP cells resistant to the cis-dichlorodiammine platinum (cisplatin) were measured by Fura-2/AM, the proliferation ability and cell cycle were measured by propidium iodide(PI) labeling cellular nuclear DNA. The results indicated that the concentration of intracellular free calcium of the sensitive A₅₄₉ cells was 2 times higher than that of the resistant A₅₄₉/DDP cells; the proliferation ability of the latter increased significantly than that of the former, the cell cycle also shortened. The proliferation ability and cell cycle of the two cell lines also clearly showed difference by decreasing or increasing their intracellular free calcium concentration if the cells were treated with BAPTA-AM or EGTA and A₂₃₁₈₇ or Thapsigargin. All of the results demonstrated that the concentration decrease of intracellular free calcium in the A₅₄₉/DDP cells resistant to cisplatin may affect the cellular proliferation, shorten the cellular cycle, which would be helpful to remain the multidrug resistance characteristics of A₅₄₉/DDP cells by specially modulating the cellular decisive G1 of cell cycle.