Human albumin (HA) is a very important blood product which requires strict quality control strategy. Acid precipitation is a key step which has a great effect on the quality of final product. Therefore, a new method based on quality by design (QbD) was proposed to investigate the feasibility of realizing online quality control with the help of near infrared spectroscopy (NIRS) and chemometrics. The pH value is the critical process parameter (CPP) in acid precipitation process, which is used as the end-point indicator. Six batches, a total of 74 samples of acid precipitation process, were simulated in our lab. Four batches were selected randomly as calibration set and remaining two batches as validation set. Then, the analysis based on material information and three different variable selection methods, including interval partial least squares regression (iPLS), competitive adaptive reweighted sampling (CARS) and correlation coe±cient (CC) were compared for eliminating irrelevant variables. Finally, iPLS was used for variables selection. The quantitative model was built up by partial least squares regression (PLSR). The values of determination coe±cients (R2c and R2p ), root mean squares error of prediction (RMSEP), root mean squares error of calibration (RMSEC) and root mean squared error of cross validation (RMSECV) were 0.969, 0.953, 0.0496, 0.0695 and 0.0826, respectively. The paired t test and repeatability test showed that the model had good prediction ability and stability. The results indicated that PLSR model could give accurate measurement of the pH value.