Introduction: Radiation from cell phones has been associated with an increased risk of cancer. The literature has reported evidence of certain biological effects resulting from exposure to various wavelengths, doses, and intensities of radiofrequency radiation. The present study aimed to evaluate the possible adverse effects of radiation from a GSM mobile phone operating at 900 MHz on human melanoma A375 cells. Material and Methods: Cellular morphology was observed under an inverted phase contrast microscope. Cell viability was determined through trypan blue dye exclusion and clonogenic assay. Moreover, flow cytometry was applied to detect DNA damage, cell cycle arrest, and reactive oxygen species (ROS) production. Cellular reduced glutathione (GSH) content was estimated by measuring the total soluble thiol. In addition, the physico-chemical changes were assessed using spectrophotometer and viscometer. Results: This study revealed that there was no change in cellular morphology and necrotic cell killing; although a small effect was observed on delayed cell death. Depletion in GSH content was noted, but ROS generation was not significantly different from that of the control group. No DNA damage was found during such exposure and there was no alteration in cell cycle distribution. In vitro evaluation of radiation effect on calf thymus DNA showed a slight perturbation in absorption spectra that was completely reversible with time. On the other hand, viscometric analysis showed no changes. Conclusion: From the findings, it can be concluded that this range of mobile phone radiation for 60 min of continuous exposure has no genotoxic impact on A375 cells.