To investigate the value of color Doppler ultrasound combined with the levels of serum alpha-fetoprotein (AFP) and creatine kinase (CK) for diagnosing pernicious placenta previa (PPP) and placenta implantation of pregnant women during the third of trimester of pregnancy. Methods: 200 pregnant women with PPP were selected in this study from October 2015 to October 2019. According to the results of intraoperative findings and postoperative pathological examination, these women were divided into group A (86 women with placenta implantation) and group B (114 women without placenta implantation). And another 78 normal pregnant women were selected in group C. All these women were given color Doppler ultrasound examination and the detection of serum AFP and CK during the third of trimester of pregnancy. The diagnostic value of serum AFP and CK combined with Doppler ultrasound examination for PPP and placenta implantation was analyzed. Results: The serum AFP and CK levels of the women in group A were significant higher than those of the women in group B and C (P<0.05). The cutoff values of the AFP level and CK level for diagnosing PPP and placenta implantation were 310.5ng/mL and 81.02U/L, respectively, and their AUC values were 0.694 and 0.728, respectively. The AUC value of combined detection AFP and CK were 0.783, which was significant higher than that of AFP detection or CK detection alone (P<0.05). The sensitivity, the negative predictive value, and the accuracy of the AFP level and CK level combined with Doppler ultrasound examination for diagnosing PPP and placenta implantation were significant higher than those of the AFP level, CK level, or Doppler ultrasound examination alone (P<0.05). The AFP level of the women with penetrating placenta was significant higher than that of the women with adhesion placenta or the women with placenta implantation (P<0.05). Conclusion: The serum AFP and CK detection combined with Doppler ultrasound examination for diagnosing PPP and placenta implantation have some value, which can effectively improve the diagnostic accuracy.