Objective To explore the effect of necroptosis inhibitor and polyethylene glycol with a molecular weight of 4 000 (PEG-4000) on the adhesion and deposition of calcium oxalate monohydrate (COM) on the surface of transformed C3H mouse kidney 1 (TCMK-1) cells. Methods TCMK-1 cells were separately treated with 400 or 800 μg/mL COM or pretreated with receptor-interacting serine/threonine-protein kinase (RIPK) 3 inhibitor GSK-872 before 400 or 800 μg/mL COM treatment. After incubation at 37 ℃ for 12 h, the crystal adhesion of TCMK-1 cells was observed under the phase inverted microscope. The cell proliferation activity was detected by cell counting kit 8 (CCK-8) method, the cell oxidative stress level was detected by 2’,7’-dichlorodihydrofluorescein diacetate (DCFH-DA) probe method, the expression of necroptosis-related proteins RIPK1, RIPK3, and phospho-mixed lineage kinase domain-like protein (p-MLKL) was detected by Western blotting, and the crystal adhesion of TCMK-1 cells was detected by inductively coupled plasma emission spectroscopy (ICP). TCMK-1 cells were divided into 3 groups and separately treated with 800 μg/mL COM, PEG-4000 solution followed by 800 μg/mL COM, or 800 μg/mL COM followed by PEG-4000 solution. After incubation at 37 ℃ for 12 h, the crystal adhesion of TCMK-1 cells was observed under the phase inverted microscope. The cell proliferation activity was detected by CCK-8 method, the oxidative stress level was detected by DCFH-DA probe method, and the surface crystal adhesion was detected by ICP method. Results At 400 μg/mL of COM, compared with the COM treated group, the GSK-872 pretreatment group showed a decrease in TCMK-1 cell crystal adhesion, an increase in cell proliferation activity (P＜0.05), and a decrease in oxidative stress level (P＜0.05). At 800 μg/mL of COM, the crystal adhesion of TCMK-1 cells in the GSK-872 pretreated group had no significant changes compared with the COM treated group, while the cell proliferation activity was increased (P＜0.05), the oxidative stress level was decreased (P＜0.05), and the expression of RIPK3 and p-MLKL was decreased (both P＜0.05). Compared with the COM treated group, the crystal adhesion of TCMK-1 cells in the PEG-4000 pretreated group was significantly decreased, with enhanced cell proliferation activity and decreased oxidative stress level (all P＜ 0.05). There were no significant changes in crystal adhesion, cell proliferation activity or oxidative stress levels between the PEG-4000 post-added group and the COM treated group (all P＞0.05). Conclusion Inhibition of necroptosis by GSK-872 can reduce the adhesion deposition of COM in cells to a certain extent, but the crystals can aggregate on the cell surface to form amorphous precipitates under high crystal load. The pre-application with PEG-4000 in the culture medium can maintain the suspension stability of COM micrograins in suspension, with less accumulation, adhesion, deposition of crystals and less oxidative stress damage of cells. Addition of PEG-4000 to TCMK-1 cells exposed to COM could not reverse the crystal adhesion, aggregation or deposition.