Cervical cancer is one of the leading life-threatening cancers around the globe. In fact, it is the fourth most common reported cancer in women with an estimate of 530,000 cases every year. In Saudi Arabia, a recent report from the Human papilloma virus (HPV) information centre has indicated annual cases of 358 diagnosed cervical cancer, placing it as the eighth most frequent cancer in the country. Such disease has been found to have a strong association with HPV infection as the primary risk factor. HPV is one of the most common sexually transmitted diseases (STDs) around the world, where certain oncogenic types of the infection can result in serious consequences in the female above 15 years of age, mainly cervical cancer. Nevertheless, there is an obvious limitation in data from Saudi Arabia regarding such infection and its complications. In Saudi Arabia, HPV vaccine has been available since 2010 for all women upon request or if prescribed by their physicians. However, despite its availability to public, statistics showed low rates of vaccine endorsement as well as Pap smear test among Saudi women. This study aimed to assess the knowledge gap and attitude of women in Makkah city towards HPV vaccine along with Pap smear screen test. Our results have shown a remarkable lack of awareness from the participants in regards to the HPV vaccine and Pap smear, although their awareness about the cervical cancer was high. The data also pointed out a possible malpractice of some physicians toward the recommendation of Pap smear test to their patients. In conclusion, there is still a clear gap in the knowledge and attitude from our participants towards the prevention measures of HPV infection and cervical cancer, which would possibly affect the roll out of HPV vaccine program. Therefore, more health promotion programs and campaign are needed to ensure success of the vaccine roll out and help avoid further complication of such disease.