The invention discloses a chalcone compound with anti-cancer activity as well as a preparation method, a preparation and application of the chalcone compound. The structure of the chalcone compound with the anti-cancer activity is as shown in the specification, in the formula, X is halogen, and R is a residue of other compounds. The preparation method comprises the following steps: according to a synthesis formula as shown in the specification, of the chalcone compound with anti-cancer activity, dissolving aromatic aldehyde and aromatic ketone in an organic solvent, under the action of a catalyst, performing backflow reaction for 3-8 hours, adjusting the pH value of a reaction liquid with diluted hydrochloric acid to 2-6, purifying, and drying, thereby obtaining a target compound, that is, the chalcone compound with anti-cancer activity. The preparation is prepared by adding the chalcone compound with anti-cancer activity into pharmaceutically acceptable auxiliaries. The application refers to application of the chalcone compound with anti-cancer activity in preparing anti-tumor medicines. The chalcone compound disclosed by the invention is a compound of a completely novel structure, has a remarkable anti-tumor function, and can be used as a potential lead compound.