Background and purpose: Highly consumption of antibiotics and their entrance into the environment has increased concerns all over the world. These compounds enter to the environment through an incomplete metabolism and a considerable amount of them cannot be removed using usual waste filtration systems. Therefore, the present study aimed to investigate the feasibility of using ultraviolet radiation (UV-A) to remove penicillin G (PENG) from aqueous phase and determining its removal efficiency. Materials and Methods: The experiments were carried out in the batch mode. The samples were assessed in a 2-liter reactor. In order to investigate the effect of UV-A radiation on the removal rate of antibiotic penicillin G (PENG), the following parameters were studied. Three concentration levels of PENG antibiotic (10,25,and 45 mg/l) were exposed to UV-A at three pH levels (3,7,11) and were evaluated at four reaction times (30,60,90, and 120 min). Antibiotic penicillin G (PENG) was determined using HPLC instrument (Waters YL9100,USA) and results analyzed using factorial design software. Results: The finding demonstrated that antibiotic removal rate increased by decreasing pH and decreasing the initial concentration of antibiotic and increasing contact time. The maximum rate of penicillin G removal occurred in acidic pH (pH=3) is as much as 38%. All of the variables in the process have been statistically significant effect (p<0.001). Conclusion: Results showed that by reducing the pH, increasing contact time and reducing the antibiotic concentration, the removal rate increases. In conclusion, photodegradation process using UV-A may enhance the rate of penicillin G degradation in polluted water and could be used as a complementary step for other chemical and biological processes to remove penicillin G from the aqueous solution. Therefore, UV-A process in conjugate with the other processes is an appropriate method for reducing antibiotic penicillin G in polluted water resources.