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Soil nutrients are essential factors that reflect farmland quality. Nitrogen, phosphorus, and potassium are essential elements for plants, while silicon is considered a “quasi-essential” element. This study investigated the spatial distribution of plant nutrients in soil in a hilly region of the Pearl River Delta in China. A total of 201 soil samples were collected from farmland topsoil (0–20 cm) for the analysis of total nitrogen (TN), available phosphorus (AP), available potassium (AK), and available silicon (ASi). The coefficients of variation ranged from 47.88% to 76.91%. The NSRs of TN, AP, AK, and ASi were 0.15, 0. 07, 0.12, and 0.13, respectively. The NSRs varied from 0.02 to 0.20. All variables exhibited weak spatial dependence (R2 < 0.5), except for TN (R2 = 0.701). After comparing the prediction accuracy of the different methods, we used the inverse distance weighting method to analyze the spatial distribution of plant nutrients in soil. The uniform spatial distribution of AK, TN overall showed a trend of increasing from northeast to southwest, and the overall spatial distribution of AP and ASi showed that the northeast was higher than the southwest. This study provides support for the delimitation of basic farmland protection areas, the formulation of land use spatial planning, and the formulation of accurate farmland protection policies.