The aim of this study was to assess the effect of sodium alginate-immobilized bacteria and ultrasonic assistance on the biodegradation of oestrogens in soil. The studied oestrogens were oestrone (E1), oestradiol (E2), oestriol (E3), 17α-ethinylestradiol (EE2), and bisphenol-A (BPA). A central composite design was developed to determine the optimal conditions of the three variables (ultrasound time, sodium alginate concentration, and amount of sodium alginate beads) for the removal of oestrogens. Moreover, the experiment utilized a quantitative structure-biodegradation relationship (QSBR) to analyze the effect of the estrogenic physicochemical properties on the enhancement of the biological degradation mechanism. The results indicated that the optimal conditions are an ultrasound time of three min, a sodium alginate concentration of 3%, and 4 g of sodium alginate beads. These conditions resulted in removal rates of 100%, 100%, 93%, 96.47, and 51.87% for E1, E2, EE2, BPA, and E3, respectively, after seven days. These rates were 1.7, 1.4, 1.3, 1.2, and 2.1 times the microbial degradation rate of the suspended state, respectively. Based on a Pearson correlation analysis, the oestrogen molecule polar surface area (PSA) and hydrophobicity (represented by logKow) were significantly related to the effect of biodegradation. An analysis of the OSBR model (with the oestrogen biodegradation rates as a dependent variable and PSA and logKow as independent variables) indicated the following: PSA negatively correlated and logKow positively correlated with oestrogen removal, and these effects were synergistic. Therefore, sodium alginate/ultrasound assistance can significantly improve the biodegradation rates of oestrogens in soil, while simultaneously adjusting other environmental conditions would influence and control the biodegradation processes of oestrogens.