Purpose: Breast cancer is the most common female malignancy and melanoma is the most lethal type of skin cancer. Traditional therapy for cancer treatment is far from satisfactory due to drug resistance and side effects, thus a search for new medicines is being emphasized. Palladium(II) complexes have been reported as anticancer potential agents. In this work, the anticancer activities and cell death induction of a new series of square-planar palladium(II) complexes were evaluated against MCF-7 and MDA-MB-435 cancer cells. Methods: MCF-7 (breast carcinoma) and MDA-MB-435 (melanoma) cells were cultivated, and treated with ligand and Pd(II) complexes. Cell growth, migration and adhesion inhibition, morphological alterations, cell death induction and, DNA interaction upon treatment were studied. Results: Pd(II) complexes exhibited both short and long-term antiproliferative effects on both cell lines, reducing by 80% cell growth in the SRB assay and abolishing long-term proliferation, estimated by the clonogenic assay. Complexes reduced significantly (p < 0.05) cell migration and adhesion when compared to the control group. Complexes induced morphological alterations in cell lines and significant (p<0.05) cellular shrinkage. Cell death was induced and the complexes were able to interact with DNA, inducing cleavage of double-stranded DNA, which may account for the complexes cytotoxic effects, observed against both MCF-7 and MDA-MB-435 cells. Conclusion: Overall, the complexes exhibited cytotoxic activities and induced cell death. These observations emphasize an anticancer role with a potential therapeutic value for Pd(II) complexes to improve the outcome of patients with breast cancer and melanoma.