Purpose: This study was done to investigate the effect of foot reflexology on vital signs, general fatigue, mood and foot fatigue in cancer patients receiving chemotherapy. Method: Data were collected from a convenience sample of 11 patients who were admitted at S and E University Hospital. Changes in systolic blood pressure (SBP), diastolic blood pressure(DBP), pulse rate(PR), general fatigue, mood status, and foot fatigue between pre and post foot reflexology were analyzed using Wilcoxon signed rank test and Friedman test at 0.05 level of significance. Results: There were significant differences in the SBP(p= .009), DBP(p=.014), PR(p=.015), general fatigue (p=.015) mood status(p=.007), and foot fatigue(p= .007) between pre and post foot reflexology. Conclusion: Foot reflexology can improve vital signs, general/foot fatigue and mood status, therefore we recommend to use foot reflexology as an effective nursing intervention in cancer patients receiving chemotherapy.